The RIT1 C-terminus associates with lipid bilayers via charge complementarity

Migliori, Amy D.; Patel, Lara A.; Neale, Chris

doi:10.1016/j.compbiolchem.2021.107437

Title: The RIT1 C-terminus associates with lipid bilayers via charge complementarity

Journal Article · Tue Jan 19 00:00:00 EST 2021 · Computational Biology and Chemistry

DOI:https://doi.org/10.1016/j.compbiolchem.2021.107437· OSTI ID:1890970

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Los Alamos National Lab. (LANL), Los Alamos, NM (United States). Center for Nonlinear Studies; Los Alamos National Lab. (LANL), Los Alamos, NM (United States). Theoretical Biology and Biophysics
Los Alamos National Lab. (LANL), Los Alamos, NM (United States). Theoretical Biology and Biophysics

RIT1 is a member of the Ras superfamily of small GTPases involved in regulation of cellular signaling. Mutations to RIT1 are involved in cancer and developmental disorders. Like many Ras subfamily members, RIT1 is localized to the plasma membrane. However, RIT1 lacks the C-terminal prenylation that helps many other subfamily members adhere to cellular membranes. For this study, we used molecular dynamics simulations to examine the mechanisms by which the C-terminal peptide (CTP) of RIT1 associates with lipid bilayers. We show that the CTP is unstructured and that its membrane interactions depend on lipid composition. While a 12-residue region of the CTP binds strongly to anionic bilayers containing phosphatidylserine lipids, the CTP termini fray from the membrane allowing for accommodation of the RIT1 globular domain at the membrane-water interface.

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Research Organization:: Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

Sponsoring Organization:: USDOE Laboratory Directed Research and Development (LDRD) Program; USDOE National Nuclear Security Administration (NNSA)

Grant/Contract Number:: 89233218CNA000001; AC5206NA25396

OSTI ID:: 1890970

Alternate ID(s):: OSTI ID: 1809776

Report Number(s):: LA-UR-19-32749

Journal Information:: Computational Biology and Chemistry, Vol. 91; ISSN 1476-9271

Publisher:: ElsevierCopyright Statement

Country of Publication:: United States

Language:: English

References (116)

Structural basis of recognition of farnesylated and methylated KRAS4b by PDEδ Dharmaiah, Srisathiyanarayanan; Bindu, Lakshman; Tran, Timothy H. Proceedings of the National Academy of Sciences, Vol. 113, Issue 44 https://doi.org/10.1073/pnas.1615316113	journal	October 2016
RA-GEF-1, a Guanine Nucleotide Exchange Factor for Rap1, Is Activated by Translocation Induced by Association with Rap1·GTP and Enhances Rap1-dependent B-Raf Activation Liao, Yanhong; Satoh, Takaya; Gao, Xianlong Journal of Biological Chemistry, Vol. 276, Issue 30 https://doi.org/10.1074/jbc.M101737200	journal	July 2001
The C-terminal end of R-Ras contains a focal adhesion targeting signal Furuhjelm, Johanna; Peränen, Johan Journal of Cell Science, Vol. 116, Issue 18 https://doi.org/10.1242/jcs.00689	journal	September 2003
The Ras superfamily at a glance Wennerberg, K. Journal of Cell Science, Vol. 118, Issue 5 https://doi.org/10.1242/jcs.01660	journal	March 2005
Ras membrane orientation and nanodomain localization generate isoform diversity Abankwa, D.; Gorfe, A. A.; Inder, K. Proceedings of the National Academy of Sciences, Vol. 107, Issue 3 https://doi.org/10.1073/pnas.0903907107	journal	January 2010
Dexamethasone-Induced Ras Protein 1 Negatively Regulates Protein Kinase C δ: Implications for Adenylyl Cyclase 2 Signaling Nguyen, Chau H.; Watts, Val J. Molecular Pharmacology, Vol. 69, Issue 5 https://doi.org/10.1124/mol.105.019133	journal	February 2006
Genomic Correlates of Immune-Cell Infiltrates in Colorectal Carcinoma Giannakis, Marios; Mu, Xinmeng Jasmine; Shukla, Sachet A. Cell Reports, Vol. 15, Issue 4 https://doi.org/10.1016/j.celrep.2016.03.075	journal	April 2016
Protein lipidation: Function and mechanism of palmitoylation Nadolski, Marissa J.; Linder, Maurine E. FEBS Journal, Vol. 274, Issue 20 https://doi.org/10.1111/j.1742-4658.2007.06056.x	journal	September 2007
Oncogenic RIT1 mutations in lung adenocarcinoma Berger, A. H.; Imielinski, M.; Duke, F. Oncogene, Vol. 33, Issue 35 https://doi.org/10.1038/onc.2013.581	journal	January 2014
Comparison of simple potential functions for simulating liquid water Jorgensen, William L.; Chandrasekhar, Jayaraman; Madura, Jeffry D. The Journal of Chemical Physics, Vol. 79, Issue 2 https://doi.org/10.1063/1.445869	journal	July 1983
Cloning and characterization of the human gene RAP2C, a novel member of Ras family, which activates transcriptional activities of SRE Guo, Zekun; Yuan, Jian; Tang, Wenwen Molecular Biology Reports, Vol. 34, Issue 3 https://doi.org/10.1007/s11033-006-9023-9	journal	April 2007
GROMACS: High performance molecular simulations through multi-level parallelism from laptops to supercomputers Abraham, Mark James; Murtola, Teemu; Schulz, Roland SoftwareX, Vol. 1-2 https://doi.org/10.1016/j.softx.2015.06.001	journal	September 2015
A Mechanism for the Partial Insertion of Protein Kinase C into Membranes Yin, Mali; Ochs, Raymond S. Biochemical and Biophysical Research Communications, Vol. 281, Issue 5 https://doi.org/10.1006/bbrc.2001.4500	journal	March 2001
K-Ras4A splice variant is widely expressed in cancer and uses a hybrid membrane-targeting motif Tsai, Frederick D.; Lopes, Mathew S.; Zhou, Mo Proceedings of the National Academy of Sciences, Vol. 112, Issue 3 https://doi.org/10.1073/pnas.1412811112	journal	January 2015
Structure of the high affinity complex of inositol trisphosphate with a phospholipase C pleckstrin homology domain Ferguson, Kathryn M.; Lemmon, Mark A.; Schlessinger, Joseph Cell, Vol. 83, Issue 6 https://doi.org/10.1016/0092-8674(95)90219-8	journal	December 1995
RERG Is a Novel ras-related, Estrogen-regulated and Growth-inhibitory Gene in Breast Cancer Finlin, Brian S.; Gau, Chia-Ling; Murphy, Gretchen A. Journal of Biological Chemistry, Vol. 276, Issue 45 https://doi.org/10.1074/jbc.M105888200	journal	November 2001
The mutational burdens and evolutionary ages of early gastric cancers are comparable to those of advanced gastric cancers: Early and advanced gastric cancer genomes Kim, Tae-Min; Jung, Seung-Hyun; Kim, Min Sung The Journal of Pathology, Vol. 234, Issue 3 https://doi.org/10.1002/path.4401	journal	August 2014
Rho family proteins: coordinating cell responses Ridley, Anne J. Trends in Cell Biology, Vol. 11, Issue 12 https://doi.org/10.1016/S0962-8924(01)02153-5	journal	December 2001
Rap2 function requires palmitoylation and recycling endosome localization Uechi, Yukiko; Bayarjargal, Maitsetseg; Umikawa, Masato Biochemical and Biophysical Research Communications, Vol. 378, Issue 4 https://doi.org/10.1016/j.bbrc.2008.11.107	journal	January 2009
Plasma membranes are asymmetric in lipid unsaturation, packing and protein shape Lorent, J. H.; Levental, K. R.; Ganesan, L. Nature Chemical Biology, Vol. 16, Issue 6 https://doi.org/10.1038/s41589-020-0529-6	journal	May 2020
Rig is a novel Ras-related protein and potential neural tumor suppressor Ellis, C. A.; Vos, M. D.; Howell, H. Proceedings of the National Academy of Sciences, Vol. 99, Issue 15 https://doi.org/10.1073/pnas.142193799	journal	July 2002
Computational Modeling Reveals that Signaling Lipids Modulate the Orientation of K-Ras4A at the Membrane Reflecting Protein Topology Li, Zhen-Lu; Buck, Matthias Structure, Vol. 25, Issue 4 https://doi.org/10.1016/j.str.2017.02.007	journal	April 2017
Mutational landscape of metastatic cancer revealed from prospective clinical sequencing of 10,000 patients Zehir, Ahmet; Benayed, Ryma; Shah, Ronak H. Nature Medicine, Vol. 23, Issue 6 https://doi.org/10.1038/nm.4333	journal	May 2017
Next-generation sequencing identifies rare variants associated with Noonan syndrome Chen, P. -C.; Yin, J.; Yu, H. -W. Proceedings of the National Academy of Sciences, Vol. 111, Issue 31 https://doi.org/10.1073/pnas.1324128111	journal	July 2014
GROMACS: A message-passing parallel molecular dynamics implementation Berendsen, H. J. C.; van der Spoel, D.; van Drunen, R. Computer Physics Communications, Vol. 91, Issue 1-3 https://doi.org/10.1016/0010-4655(95)00042-E	journal	September 1995
Ezrin contains cytoskeleton and membrane binding domains accounting for its proposed role as a membrane-cytoskeletal linker. Algrain, M.; Turunen, O.; Vaheri, A. Journal of Cell Biology, Vol. 120, Issue 1 https://doi.org/10.1083/jcb.120.1.129	journal	January 1993
Indirect association of ezrin with F-actin: isoform specificity and calcium sensitivity. Shuster, C. B.; Herman, I. M. Journal of Cell Biology, Vol. 128, Issue 5 https://doi.org/10.1083/jcb.128.5.837	journal	March 1995
An Acylation Cycle Regulates Localization and Activity of Palmitoylated Ras Isoforms Rocks, O. Science, Vol. 307, Issue 5716 https://doi.org/10.1126/science.1105654	journal	March 2005
Novel recurrent mutations in the RAS-like GTP-binding gene RIT1 in myeloid malignancies Gómez-Seguí, I.; Makishima, H.; Jerez, A. Leukemia, Vol. 27, Issue 9 https://doi.org/10.1038/leu.2013.179	journal	June 2013
Imaging Activation of Two Ras Isoforms Simultaneously in a Single Cell Peyker, Anna; Rocks, Oliver; Bastiaens, Philippe I. H. ChemBioChem, Vol. 6, Issue 1 https://doi.org/10.1002/cbic.200400280	journal	January 2005
Human RAS Superfamily Proteins and Related GTPases Colicelli, J. Science Signaling, Vol. 2004, Issue 250 https://doi.org/10.1126/stke.2502004re13	journal	September 2004
The integrated landscape of driver genomic alterations in glioblastoma Frattini, Veronique; Trifonov, Vladimir; Chan, Joseph Minhow Nature Genetics, Vol. 45, Issue 10 https://doi.org/10.1038/ng.2734	journal	August 2013
Optimization of the Additive CHARMM All-Atom Protein Force Field Targeting Improved Sampling of the Backbone ϕ, ψ and Side-Chain χ ₁ and χ ₂ Dihedral Angles Best, Robert B.; Zhu, Xiao; Shim, Jihyun Journal of Chemical Theory and Computation, Vol. 8, Issue 9 https://doi.org/10.1021/ct300400x	journal	August 2012
Dictionary of protein secondary structure: Pattern recognition of hydrogen-bonded and geometrical features Kabsch, Wolfgang; Sander, Christian Biopolymers, Vol. 22, Issue 12 https://doi.org/10.1002/bip.360221211	journal	December 1983
Oncogenic K-Ras Binds to an Anionic Membrane in Two Distinct Orientations: A Molecular Dynamics Analysis Prakash, Priyanka; Zhou, Yong; Liang, Hong Biophysical Journal, Vol. 110, Issue 5 https://doi.org/10.1016/j.bpj.2016.01.019	journal	March 2016
Rho family GTPases Hall, Alan Biochemical Society Transactions, Vol. 40, Issue 6 https://doi.org/10.1042/BST20120103	journal	November 2012
The detection and classification of membrane-spanning proteins Klein, Petr; Kanehisa, Minoru; DeLisi, Charles Biochimica et Biophysica Acta (BBA) - Biomembranes, Vol. 815, Issue 3 https://doi.org/10.1016/0005-2736(85)90375-X	journal	May 1985
Genotype and phenotype in patients with Noonan syndrome and a RIT1 mutation Kouz, Karim; Lissewski, Christina; Spranger, Stephanie Genetics in Medicine, Vol. 18, Issue 12 https://doi.org/10.1038/gim.2016.32	journal	April 2016
Regulation of Ca2+ channel expression at the cell surface by the small G-protein kir/Gem Béguin, Pascal; Nagashima, Kazuaki; Gonoi, Tohru Nature, Vol. 411, Issue 6838 https://doi.org/10.1038/35079621	journal	June 2001
Polymorphic transitions in single crystals: A new molecular dynamics method Parrinello, M.; Rahman, A. Journal of Applied Physics, Vol. 52, Issue 12 https://doi.org/10.1063/1.328693	journal	December 1981
A series of PDB-related databanks for everyday needs Touw, Wouter G.; Baakman, Coos; Black, Jon Nucleic Acids Research, Vol. 43, Issue D1 https://doi.org/10.1093/nar/gku1028	journal	October 2014
Cloning and characterization of a novel small monomeric GTPase, RasL10B, with tumor suppressor potential Zou, Huafei; Hu, Lide; Li, Jixi Biotechnology Letters, Vol. 28, Issue 23 https://doi.org/10.1007/s10529-006-9176-6	journal	September 2006
The spontaneous insertion of proteins into and across membranes: The helical hairpin hypothesis Engelman, D. M.; Steitz, T. A. Cell, Vol. 23, Issue 2 https://doi.org/10.1016/0092-8674(81)90136-7	journal	February 1981
R-Ras interacts with filamin a to maintain endothelial barrier function Griffiths, G. S.; Grundl, M.; Allen, J. S. Journal of Cellular Physiology, Vol. 226, Issue 9 https://doi.org/10.1002/jcp.22565	journal	June 2011
Rasd1, a small G protein with a big role in the hypothalamic response to neuronal activation Greenwood, Michael P.; Greenwood, Mingkwan; Mecawi, Andre S. Molecular Brain, Vol. 9, Issue 1 https://doi.org/10.1186/s13041-015-0182-2	journal	January 2016
PIP2 Influences the Conformational Dynamics of Membrane-Bound KRAS4b McLean, Mark A.; Stephen, Andrew G.; Sligar, Stephen G. Biochemistry, Vol. 58, Issue 33 https://doi.org/10.1021/acs.biochem.9b00395	journal	July 2019
Rasd1 Modulates the Coactivator Function of NonO in the Cyclic AMP Pathway Ong, Shufen Angeline; Tan, Jen Jen; Tew, Wai Loon PLoS ONE, Vol. 6, Issue 9 https://doi.org/10.1371/journal.pone.0024401	journal	September 2011
The Guanine Nucleotide-Binding Switch in Three Dimensions Vetter, I. R. Science, Vol. 294, Issue 5545 https://doi.org/10.1126/science.1062023	journal	November 2001
K- and N-Ras Are Geranylgeranylated in Cells Treated with Farnesyl Protein Transferase Inhibitors Whyte, David B.; Kirschmeier, Paul; Hockenberry, Tish N. Journal of Biological Chemistry, Vol. 272, Issue 22 https://doi.org/10.1074/jbc.272.22.14459	journal	May 1997
All ras proteins are polyisoprenylated but only some are palmitoylated Hancock, John F.; Magee, Anthony I.; Childs, Julie E. Cell, Vol. 57, Issue 7 https://doi.org/10.1016/0092-8674(89)90054-8	journal	June 1989
Sequence dependence of protein isoprenylation Moores, S. L.; Schaber, M. D.; Mosser, S. D. Journal of Biological Chemistry, Vol. 266, Issue 22 https://doi.org/10.1016/S0021-9258(18)98729-6	journal	August 1991
Evolution of the rab family of small GTP-binding proteins Pereira-Leal, José B.; Seabra, Miguel C. Journal of Molecular Biology, Vol. 313, Issue 4 https://doi.org/10.1006/jmbi.2001.5072	journal	November 2001
VMD: Visual molecular dynamics Humphrey, William; Dalke, Andrew; Schulten, Klaus Journal of Molecular Graphics, Vol. 14, Issue 1 https://doi.org/10.1016/0263-7855(96)00018-5	journal	February 1996
ARHI is a Ras-related small G-protein with a novel N-terminal extension that inhibits growth of ovarian and breast cancers Luo, Robert Z.; Fang, Xianjun; Marquez, Rebecca Oncogene, Vol. 22, Issue 19 https://doi.org/10.1038/sj.onc.1206380	journal	May 2003
Biochemical Classification of Disease-associated Mutants of RAS-like Protein Expressed in Many Tissues (RIT1) Fang, Zhenhao; Marshall, Christopher B.; Yin, Jiani C. Journal of Biological Chemistry, Vol. 291, Issue 30 https://doi.org/10.1074/jbc.M116.714196	journal	July 2016
A polybasic domain or palmitoylation is required in addition to the CAAX motif to localize p21ras to the plasma membrane Hancock, John F.; Paterson, Hugh; Marshall, Christopher J. Cell, Vol. 63, Issue 1 https://doi.org/10.1016/0092-8674(90)90294-O	journal	October 1990
Roles played by Ras subfamily proteins in the cell and developmental biology of microorganisms Weeks, Gerald; Spiegelman, George B. Cellular Signalling, Vol. 15, Issue 10 https://doi.org/10.1016/S0898-6568(03)00073-1	journal	October 2003
Rit, a non-lipid-modified Ras-related protein, transforms NIH3T3 cells without activating the ERK, JNK, p38 MAPK or PI3K/Akt pathways Rusyn, Elena V.; Reynolds, Evangeline R.; Shao, Haipeng Oncogene, Vol. 19, Issue 41 https://doi.org/10.1038/sj.onc.1203836	journal	September 2000
Novel small GTPase M-Ras participates in reorganization of actin cytoskeleton Matsumoto, Ken; Asano, Takuya; Endo, Takeshi Oncogene, Vol. 15, Issue 20 https://doi.org/10.1038/sj.onc.1201416	journal	November 1997
Rasl11b Knock Down in Zebrafish Suppresses One-Eyed-Pinhead Mutant Phenotype Pézeron, Guillaume; Lambert, Guillaume; Dickmeis, Thomas PLoS ONE, Vol. 3, Issue 1 https://doi.org/10.1371/journal.pone.0001434	journal	January 2008
Gem: an induced, immediate early protein belonging to the Ras family Maguire, J.; Santoro, T.; Jensen, P. Science, Vol. 265, Issue 5169 https://doi.org/10.1126/science.7912851	journal	July 1994
The GTPase Rem2 regulates synapse development and dendritic morphology Ghiretti, Amy E.; Paradis, Suzanne Developmental Neurobiology, Vol. 71, Issue 5 https://doi.org/10.1002/dneu.20868	journal	April 2011
The Ras branch of small Gtpases: Ras family members don’t fall far from the tree Reuther, Gary W.; Der, Channing J. Current Opinion in Cell Biology, Vol. 12, Issue 2 https://doi.org/10.1016/S0955-0674(99)00071-X	journal	April 2000
Prenyl group identification of rap2 proteins: a ras superfamily member other than ras that is farnesylated Farrell, F. X.; Yamamoto, K.; Lapetina, E. G. Biochemical Journal, Vol. 289, Issue 2 https://doi.org/10.1042/bj2890349	journal	January 1993
P-LINCS: A Parallel Linear Constraint Solver for Molecular Simulation Hess, Berk Journal of Chemical Theory and Computation, Vol. 4, Issue 1 https://doi.org/10.1021/ct700200b	journal	December 2007
Activating Mutations of RRAS2 Are a Rare Cause of Noonan Syndrome Capri, Yline; Flex, Elisabetta; Krumbach, Oliver H. F. The American Journal of Human Genetics, Vol. 104, Issue 6 https://doi.org/10.1016/j.ajhg.2019.04.013	journal	June 2019
PI(3,4,5)P3 and PI(4,5)P2 Lipids Target Proteins with Polybasic Clusters to the Plasma Membrane Heo, W. D.; Inoue, T.; Park, W. S. Science, Vol. 314, Issue 5804 https://doi.org/10.1126/science.1134389	journal	December 2006
Localization of RalB signaling at endomembrane compartments and its modulation by autophagy Singh, Manish Kumar; Martin, Alexandre P. J.; Joffre, Carine Scientific Reports, Vol. 9, Issue 1 https://doi.org/10.1038/s41598-019-45443-1	journal	June 2019
Nuclear Localization of Endogenous RGK Proteins and Modulation of Cell Shape Remodeling by Regulated Nuclear Transport Mahalakshmi, Ramasubbu N.; Ng, Mei Yong; Guo, Ke Traffic, Vol. 8, Issue 9 https://doi.org/10.1111/j.1600-0854.2007.00599.x	journal	May 2007
Chromatin association and regulation of rDNA transcription by the Ras-family protein RasL11a Pistoni, Mariaelena; Verrecchia, Alessandro; Doni, Mirko The EMBO Journal, Vol. 29, Issue 7 https://doi.org/10.1038/emboj.2010.16	journal	February 2010
Spectrum of mutations and genotype–phenotype analysis in Noonan syndrome patients with RIT1 mutations Yaoita, Masako; Niihori, Tetsuya; Mizuno, Seiji Human Genetics, Vol. 135, Issue 2 https://doi.org/10.1007/s00439-015-1627-5	journal	December 2015
Roles of palmitoylation and the KIKK membrane-targeting motif in leukemogenesis by oncogenic KRAS4A Zhao, Huanbin; Liu, Ping; Zhang, Ruihong Journal of Hematology & Oncology, Vol. 8, Issue 1 https://doi.org/10.1186/s13045-015-0226-1	journal	December 2015
A novel approach to tag and identify geranylgeranylated proteins Chan, Lai N.; Hart, Courtenay; Guo, Lea ELECTROPHORESIS, Vol. 30, Issue 20 https://doi.org/10.1002/elps.200900259	journal	October 2009
Palmitoylation of R-Ras by human DHHC19, a palmitoyl transferase with a CaaX box Baumgart, Florian; Corral-Escariz, María; Pérez-Gil, Jesús Biochimica et Biophysica Acta (BBA) - Biomembranes, Vol. 1798, Issue 3 https://doi.org/10.1016/j.bbamem.2010.01.002	journal	March 2010
Contribution of RIT1 mutations to the pathogenesis of Noonan syndrome: Four new cases and further evidence of heterogeneity Gos, Monika; Fahiminiya, Somayyeh; Poznański, Jarosław American Journal of Medical Genetics Part A, Vol. 164, Issue 9 https://doi.org/10.1002/ajmg.a.36646	journal	June 2014
COSMIC: exploring the world's knowledge of somatic mutations in human cancer Forbes, Simon A.; Beare, David; Gunasekaran, Prasad Nucleic Acids Research, Vol. 43, Issue D1 https://doi.org/10.1093/nar/gku1075	journal	October 2014
Ras trafficking, localization and compartmentalized signalling Prior, Ian A.; Hancock, John F. Seminars in Cell & Developmental Biology, Vol. 23, Issue 2 https://doi.org/10.1016/j.semcdb.2011.09.002	journal	April 2012
Membrane-Bound Ras as a Conformational Clock Gorfe, Alemayehu A.; Sligar, Stephen G. Biophysical Journal, Vol. 118, Issue 5 https://doi.org/10.1016/j.bpj.2020.01.011	journal	March 2020
Posttranslationally processed structure of the human platelet protein smg p21B: evidence for geranylgeranylation and carboxyl methylation of the C-terminal cysteine. Kawata, M.; Farnsworth, C. C.; Yoshida, Y. Proceedings of the National Academy of Sciences, Vol. 87, Issue 22 https://doi.org/10.1073/pnas.87.22.8960	journal	November 1990
Update of the CHARMM All-Atom Additive Force Field for Lipids: Validation on Six Lipid Types Klauda, Jeffery B.; Venable, Richard M.; Freites, J. Alfredo The Journal of Physical Chemistry B, Vol. 114, Issue 23 https://doi.org/10.1021/jp101759q	journal	June 2010
Oncogenic and RASopathy-associated K-RAS mutations relieve membrane-dependent occlusion of the effector-binding site Mazhab-Jafari, Mohammad T.; Marshall, Christopher B.; Smith, Matthew J. Proceedings of the National Academy of Sciences, Vol. 112, Issue 21 https://doi.org/10.1073/pnas.1419895112	journal	May 2015
Identification and biochemical characterization of Rap2C, a new member of the Rap family of small GTP-binding proteins Paganini, S.; Guidetti, G.; Catricala, S. Biochimie, Vol. 88, Issue 3-4 https://doi.org/10.1016/j.biochi.2005.08.007	journal	March 2006
The Ras protein superfamily: Evolutionary tree and role of conserved amino acids Rojas, Ana Maria; Fuentes, Gloria; Rausell, Antonio The Journal of Cell Biology, Vol. 196, Issue 2 https://doi.org/10.1083/jcb.201103008	journal	January 2012
Dual chemical probes enable quantitative system-wide analysis of protein prenylation and prenylation dynamics Storck, Elisabeth M.; Morales-Sanfrutos, Julia; Serwa, Remigiusz A. Nature Chemistry, Vol. 11, Issue 6 https://doi.org/10.1038/s41557-019-0237-6	journal	April 2019
CHARMM-GUI Membrane Builder for Mixed Bilayers and Its Application to Yeast Membranes Jo, Sunhwan; Lim, Joseph B.; Klauda, Jeffery B. Biophysical Journal, Vol. 97, Issue 1 https://doi.org/10.1016/j.bpj.2009.04.013	journal	July 2009
The chronological sequence of somatic mutations in early gastric carcinogenesis inferred from multiregion sequencing of gastric adenomas Lim, Chul-Hyun; Cho, Yu Kyung; Kim, Sang Woo Oncotarget, Vol. 7, Issue 26 https://doi.org/10.18632/oncotarget.9250	journal	May 2016
Association of Rap1a and Rap1b proteins with late endocytic/phagocytic compartments and Rap2a with the Golgi complex Pizon, V.; Desjardins, M.; Bucci, C. Journal of Cell Science, Vol. 107, Issue 6 https://doi.org/10.1242/jcs.107.6.1661	journal	June 1994
SHOC2–MRAS–PP1 complex positively regulates RAF activity and contributes to Noonan syndrome pathogenesis Young, Lucy C.; Hartig, Nicole; Boned del Río, Isabel Proceedings of the National Academy of Sciences, Vol. 115, Issue 45 https://doi.org/10.1073/pnas.1720352115	journal	October 2018
Differential requirement of CAAX-mediated posttranslational processing for Rheb localization and signaling Hanker, A. B.; Mitin, N.; Wilder, R. S. Oncogene, Vol. 29, Issue 3 https://doi.org/10.1038/onc.2009.336	journal	October 2009
The Tumor Suppressor DiRas3 Forms a Complex with H-Ras and C-RAF Proteins and Regulates Localization, Dimerization, and Kinase Activity of C-RAF Baljuls, Angela; Beck, Matthias; Oenel, Ayla Journal of Biological Chemistry, Vol. 287, Issue 27 https://doi.org/10.1074/jbc.M112.343780	journal	June 2012
Gain-of-Function Mutations in RIT1 Cause Noonan Syndrome, a RAS/MAPK Pathway Syndrome Aoki, Yoko; Niihori, Tetsuya; Banjo, Toshihiro The American Journal of Human Genetics, Vol. 93, Issue 1 https://doi.org/10.1016/j.ajhg.2013.05.021	journal	July 2013
Rem2, a new member of the Rem/Rad/Gem/Kir family of Ras-related GTPases Finlin, Brian S.; Shao, Haipeng; Kadono-Okuda, Keiko Biochemical Journal, Vol. 347, Issue 1 https://doi.org/10.1042/bj3470223	journal	March 2000
A CAAX or a CAAL motif and a second signal are sufficient for plasma membrane targeting of ras proteins. Hancock, J. F.; Cadwallader, K.; Paterson, H. The EMBO Journal, Vol. 10, Issue 13 https://doi.org/10.1002/j.1460-2075.1991.tb04979.x	journal	December 1991
Clinical Sequencing Defines the Genomic Landscape of Metastatic Colorectal Cancer Yaeger, Rona; Chatila, Walid K.; Lipsyc, Marla D. Cancer Cell, Vol. 33, Issue 1 https://doi.org/10.1016/j.ccell.2017.12.004	journal	January 2018
Rit subfamily small GTPases: Regulators in neuronal differentiation and survival Shi, Geng-Xian; Cai, Weikang; Andres, Douglas A. Cellular Signalling, Vol. 25, Issue 10 https://doi.org/10.1016/j.cellsig.2013.06.002	journal	October 2013
Calmodulin disrupts plasma membrane localization of farnesylated KRAS4b by sequestering its lipid moiety Grant, Benjamin M. M.; Enomoto, Masahiro; Back, Sung-In Science Signaling, Vol. 13, Issue 625 https://doi.org/10.1126/scisignal.aaz0344	journal	March 2020
Mapping the Hallmarks of Lung Adenocarcinoma with Massively Parallel Sequencing Imielinski, Marcin; Berger, Alice H.; Hammerman, Peter S. Cell, Vol. 150, Issue 6 https://doi.org/10.1016/j.cell.2012.08.029	journal	September 2012
RAS-related GTPases DIRAS1 and DIRAS2 induce autophagic cancer cell death and are required for autophagy in murine ovarian cancer cells Sutton, Margie N.; Yang, Hailing; Huang, Gilbert Y. Autophagy, Vol. 14, Issue 4 https://doi.org/10.1080/15548627.2018.1427022	journal	March 2018
Differential Membrane Localization of ERas and Rheb, Two Ras-related Proteins Involved in the Phosphatidylinositol 3-Kinase/mTOR Pathway Takahashi, Kazutoshi; Nakagawa, Masato; Young, Stephen G. Journal of Biological Chemistry, Vol. 280, Issue 38 https://doi.org/10.1074/jbc.M506280200	journal	September 2005
Automated Builder and Database of Protein/Membrane Complexes for Molecular Dynamics Simulations Jo, Sunhwan; Kim, Taehoon; Im, Wonpil PLoS ONE, Vol. 2, Issue 9 https://doi.org/10.1371/journal.pone.0000880	journal	September 2007
Overexpression of Rad Inhibits Glucose Uptake in Cultured Muscle and Fat Cells Moyers, Julie S.; Bilan, Philip J.; Reynet, Christine Journal of Biological Chemistry, Vol. 271, Issue 38 https://doi.org/10.1074/jbc.271.38.23111	journal	September 1996
The molecular functions of RIT1 and its contribution to human disease Van, Richard; Cuevas-Navarro, Antonio; Castel, Pau Biochemical Journal, Vol. 477, Issue 15 https://doi.org/10.1042/BCJ20200442	journal	August 2020
Targeting of the small GTPase Rap2b, but not Rap1b, to lipid rafts is promoted by palmitoylation at Cys176 and Cys177 and is required for efficient protein activation in human platelets Canobbio, Ilaria; Trionfini, Piera; Guidetti, Gianni F. Cellular Signalling, Vol. 20, Issue 9 https://doi.org/10.1016/j.cellsig.2008.05.016	journal	September 2008
The Ran GTPase regulates mitotic spindle assembly Kalab, Petr; Pu, Robert T.; Dasso, Mary Current Biology, Vol. 9, Issue 9 https://doi.org/10.1016/S0960-9822(99)80213-9	journal	May 1999
Whole-genome landscapes of major melanoma subtypes Hayward, Nicholas K.; Wilmott, James S.; Waddell, Nicola Nature, Vol. 545, Issue 7653 https://doi.org/10.1038/nature22071	journal	May 2017
The GTPase superfamily: a conserved switch for diverse cell functions Bourne, Henry R.; Sanders, David A.; McCormick, Frank Nature, Vol. 348, Issue 6297 https://doi.org/10.1038/348125a0	journal	November 1990
Rin, a Neuron-Specific and Calmodulin-Binding Small G-Protein, and Rit Define a Novel Subfamily of Ras Proteins Lee, Ching-Hsien J.; Della, Neil G.; Chew, Christina E. The Journal of Neuroscience, Vol. 16, Issue 21 https://doi.org/10.1523/JNEUROSCI.16-21-06784.1996	journal	November 1996
ABHD17 proteins are novel protein depalmitoylases that regulate N-Ras palmitate turnover and subcellular localization Lin, David Tse Shen; Conibear, Elizabeth eLife, Vol. 4 https://doi.org/10.7554/eLife.11306	journal	December 2015
RRP22 Is a Farnesylated, Nucleolar, Ras-Related Protein with Tumor Suppressor Potential Elam, Candice; Hesson, Luke; Vos, Michele D. Cancer Research, Vol. 65, Issue 8 https://doi.org/10.1158/0008-5472.CAN-04-0749	journal	April 2005
A smooth particle mesh Ewald method Essmann, Ulrich; Perera, Lalith; Berkowitz, Max L. The Journal of Chemical Physics, Vol. 103, Issue 19 https://doi.org/10.1063/1.470117	journal	November 1995
The Ran GTPase: Theme and Variations Dasso, Mary Current Biology, Vol. 12, Issue 14 https://doi.org/10.1016/S0960-9822(02)00970-3	journal	July 2002
Divergent Roles of CAAX Motif-signaled Posttranslational Modifications in the Regulation and Subcellular Localization of Ral GTPases Gentry, Leanna R.; Nishimura, Akiyuki; Cox, Adrienne D. Journal of Biological Chemistry, Vol. 290, Issue 37 https://doi.org/10.1074/jbc.M115.656710	journal	September 2015
Protein lipidation in cell signaling Casey, P. Science, Vol. 268, Issue 5208 https://doi.org/10.1126/science.7716512	journal	April 1995
The Plasma Membrane as a Competitive Inhibitor and Positive Allosteric Modulator of KRas4B Signaling Neale, Chris; García, Angel E. Biophysical Journal, Vol. 118, Issue 5 https://doi.org/10.1016/j.bpj.2019.12.039	journal	March 2020
The role of G-domain orientation and nucleotide state on the Ras isoform-specific membrane interaction Kapoor, Shobhna; Weise, Katrin; Erlkamp, Mirko European Biophysics Journal, Vol. 41, Issue 10 https://doi.org/10.1007/s00249-012-0841-5	journal	August 2012
Membrane Localization and Flexibility of a Lipidated Ras Peptide Studied by Molecular Dynamics Simulations Gorfe, Alemayehu A.; Pellarin, Riccardo; Caflisch, Amedeo Journal of the American Chemical Society, Vol. 126, Issue 46 https://doi.org/10.1021/ja046607n	journal	November 2004

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