Abstract
This article describes the role of protein fragments encoded by individual exons. Structural analysis of the hydrophobic core on the basis of the “fuzzy oil drop” model – in whole molecules as well as in fragments encoded by specific exons – indicates that, in each protein, at least one exon encodes a fragment, which is consistent with the theoretical distribution of hydrophobicity density. Quantitative assessment of the properties of such exons in selected proteins enables the model to be applied in identifying the structural (stabilizing) role of polypeptide chains encoded by individual exons. This is viewed as a preliminary step toward future exploitation of this technique in studying the alternative splicing phenomenon.
We wish to thank Piotr Nowakowski for the editorial work and Anna Śmietańska for the technical support. The work was supported financially by the Jagiellonian University Medical College under grants no. K/ZDS/001531 and K/ZDS/002907.
References
1. Kauzmann W. Some factors in the interpretation of protein denaturation. Adv Protein Chem 1959;14:1–63.10.1016/S0065-3233(08)60608-7Search in Google Scholar
2. Schmitz J, Brosius J. Exonization of transposed elements: a challenge and opportunity for evolution. Biochimie 2011;93:1928–34.10.1016/j.biochi.2011.07.014Search in Google Scholar PubMed
3. Maniatis T, Tasic B. Alternative pre-mRNA splicing and proteome expansion in metazoans. Nature 2002 418: 236–43.10.1038/418236aSearch in Google Scholar PubMed
4. Chang WC, Chen HH, Tarn WY. Alternative splicing of U12-type introns. Front Biosci 2008;13:1681–90.10.2741/2791Search in Google Scholar PubMed
5. Black DL. Mechanisms of alternative pre-messenger RNA splicing. Annu Rev Biochem 2003;72:291–336.10.1146/annurev.biochem.72.121801.161720Search in Google Scholar PubMed
6. Gelly JC, Lin HY, de Brevern AG, Chuang TJ, Chen FC. Selective constraint on human pre-mRNA splicing by protein structural properties. Genome Biol Evol 2012;4:966–75.10.1093/gbe/evs071Search in Google Scholar PubMed PubMed Central
7. Muhammad N, Dworeck T, Fioroni M, Schwaneberg U. Engineering of the E. coli outer membrane protein FhuA to overcome the hydrophobic mismatch in thick polymeric membranes. J Nanobiotechnol 2011;9:8.10.1186/1477-3155-9-8Search in Google Scholar PubMed PubMed Central
8. Neklesa TK, Tae HS, Schneekloth AR, Stulberg MJ, Corson TW, Sundberg TB, et al. Small-molecule hydrophobic tagging-induced degradation of HaloTag fusion proteins. Nat Chem Biol 2011;7:538–43.10.1038/nchembio.597Search in Google Scholar PubMed PubMed Central
9. Siglioccolo A, Paiardini A, Piscitelli M, Pascarella S. Structural adaptation of extreme halophilic proteins through decrease of conserved hydrophobic contact surface. BMC Struct Biol 2011;11:50.10.1186/1472-6807-11-50Search in Google Scholar PubMed PubMed Central
10. Li L, Zhang Y, Zou L, Li C, Yu B, Zheng X, et al. An ensemble classifier for eukaryotic protein subcellular location prediction using gene ontology categories and amino acid hydrophobicity. PLoS One 2012;7:e31057.10.1371/journal.pone.0031057Search in Google Scholar PubMed PubMed Central
11. Shao Q, Wei H, Gao YQ. Effects of turn stability and side-chain hydrophobicity on the folding of β-structures. J Mol Biol 2010;402:595–609.10.1016/j.jmb.2010.08.037Search in Google Scholar
12. Piwowar M, Krzysztof P, Piotr P. ExonVisualiser – application for visualization exon units in 2D and 3D protein structures. Bioinformation 2012;8:1280–2.10.6026/97320630081280Search in Google Scholar
13. Biswas KM, DeVido DR, Dorsey JG. Evaluation of methods for measuring amino acid hydrophobicities and interactions. J Chromatogr A 2003;1000:637–55.10.1016/S0021-9673(03)00182-1Search in Google Scholar
14. Kyte J, Doolittle RF. A simple method for displaying the hydropathic character of a protein. J Mol Biol 1982;157:105–32.10.1016/0022-2836(82)90515-0Search in Google Scholar
15. Eisenberg D. Three-dimensional structure of membrane and surface proteins. Annu Rev Biochem 1984;53:595–623.10.1146/annurev.bi.53.070184.003115Search in Google Scholar
16. Rose GD, Wolfenden R. Hydrogen bonding, hydrophobicity, packing, and protein folding. Annu Rev Biomol Struct 1993;22:381–415.10.1146/annurev.bb.22.060193.002121Search in Google Scholar
17. Janin J. Surface and inside volumes in globular proteins. Nature 1979;277:491–2.10.1038/277491a0Search in Google Scholar
18. Rose GD, Geselowitz AR, Lesser GJ, Lee RH, Zehfus MH. Hydrophobicity of amino acid residues in globular proteins. Science 1985;229:834–8.10.1126/science.4023714Search in Google Scholar
19. Wolfenden R, Andersson L, Cullis PM, Southgate CC. Affinities of amino acid side chains for solvent water. Biochemistry 1981;20:849–55.10.1021/bi00507a030Search in Google Scholar
20. Aboderin A. An empirical hydrophobicity scale for α-amino-acids and some of its applications. Int J Biochem 1971;2:537–44.10.1016/0020-711X(71)90023-1Search in Google Scholar
21. Konieczny L, Brylinski M, Roterman I. Gauss-function-based model of hydrophobicity density in proteins. In Silico Biol 2006;6:15–22.Search in Google Scholar
22. Levitt M. A simplifed representation of protein conformations for rapid simulation of protein folding. J Mol Biol 1976;104:59–107.10.1016/0022-2836(76)90004-8Search in Google Scholar
23. Kullback S, Leibler RA. On Information and Sufficiency. Ann Math Stat 1951;22:79–86.10.1214/aoms/1177729694Search in Google Scholar
24. PDBsum. Available from: http://www.ebi.ac.uk/pdbsum/. Accessed on 21 January, 2013.Search in Google Scholar
25. Banach M, Konieczny L, Roterman I. Ligand-binding-site recognition. In: Roterman-Konieczna I, editor. Protein folding in silico. Oxford, UK: Woodhead Publishing, 2012:78–94.Search in Google Scholar
26. Piwowar M, Banach M, Konieczny L, Roterman I. Hydrophobic core formation in protein complex. J Biomol Struct Dyn 2013. DOI: 10.1080/07391102.2013.801784 [Epub ahead of print].10.1080/07391102.2013.801784Search in Google Scholar PubMed
27. Piwowar M, Banach M, Konieczny L, Chomilier J, Roterman I. Structural role of exons in haemoglobin. Bio-Algorithms Med-Syst 2013;9:81–90.10.1515/bams-2013-0009Search in Google Scholar
28. Piwowar M, Banach M, Konieczny L, Roterman I. Structural role of exon-coded fragments of polypeptide chains in selected enzymes. J Theor Biol 2013. DOI: 10.1016/j.jtbi.2013.07.016 [Epub ahead of print].10.1016/j.jtbi.2013.07.016Search in Google Scholar PubMed
29. Krishna Kumar K, Dickson CF, Weiss MJ, Mackay JP, Gell DA. AHSP (α-haemoglobin-stabilizing protein) stabilizes apo-α-haemoglobin in a partially folded state. Biochem J 2010;432:275–82.10.1042/BJ20100642Search in Google Scholar PubMed PubMed Central
30. Nasimuzzaman M, Khandros E, Wang X, Kong Y, Zhao H, Weiss D, et al. Analysis of alpha hemoglobin stabilizing protein overexpression in murine β-thalassemia. Am J Hematol 2010;85:820–2.10.1002/ajh.21829Search in Google Scholar PubMed PubMed Central
31. Yu X, Kong Y, Dore LC, Abdulmalik O, Katein AM, Zhou S, et al. An erythroid chaperone that facilitates folding of α-globin subunits for hemoglobin synthesis. J Clin Invest 2007;117: 1856–65.10.1172/JCI31664Search in Google Scholar PubMed PubMed Central
32. Brillet T, Baudin-Creuza V, Vasseur C, Domingues-Hamdi ED, Kiger L, Wajcman H, et al. α-Hemoglobin stabilizing protein (AHSP), a kinetic scheme of the action of a human mutant, AHSPV56G. J Biol Chem 2010;285:17986–92.10.1074/jbc.M109.098491Search in Google Scholar PubMed PubMed Central
33. Strandberg B. Chapter 1: building the ground for the first two protein structures: myoglobin and haemoglobin. J Mol Biol 2009;392:2–10.10.1016/j.jmb.2009.05.087Search in Google Scholar PubMed
34. Mollan TL, Yu X, Weiss MJ, Olson JS. The role of alpha-hemoglobin stabilizing protein in redox chemistry, denaturation, and hemoglobin assembly. Antioxid Redox Signal 2010;12:219–31.10.1089/ars.2009.2780Search in Google Scholar PubMed PubMed Central
35. Pesce A, Milani M, Nardini M, Bolognesi M. Mapping heme-ligand tunnels in group I truncated(2/2) hemoglobins. Methods Enzymol 2008;36:303–15.10.1016/S0076-6879(08)36017-0Search in Google Scholar
36. Prymula K, Jadczyk T, Roterman I. Catalytic residues in hydrolases: analysis of methods designed for ligand-binding site prediction. J Comput Aided Mol Des 2011;25:117–33.10.1007/s10822-010-9402-0Search in Google Scholar PubMed PubMed Central
37. Pan Q, Shai O, Lee LJ, Frey BJ, Blencowe BJ. (2008) Deep surveying of alternative splicing complexity in the human transcriptome by high-throughput sequencing. Nat Genet 2008;40:1413–5.10.1038/ng.259Search in Google Scholar PubMed
38. Roterman I, Konieczny L, Jurkowski W, Prymula K, Banach M. Two-intermediate model to characterize the structure of fast-folding proteins. J Theor Biol 2011;283:60–70.10.1016/j.jtbi.2011.05.027Search in Google Scholar PubMed
39. Banach M, Prymula K, Jurkowski W, Konieczny L, Roterman I. Fuzzy oil drop model to interpret the structure of antifreeze proteins and their mutants. J Mol Model 2012;18:229–37.10.1007/s00894-011-1033-4Search in Google Scholar PubMed PubMed Central
40. Banach M, Marchewka D, Piwowar M, Roterman I. The divergence entropy characterizing the internal force field in proteins. In: Roterman-Konieczna I, editor. Protein folding in silico. Oxford, UK: Woodhead Publishing, 2012:55–78.Search in Google Scholar
41. Alejster P, Banach M, Jurkowski W, Marchewka D, Roterman I. Comparative analysis of techniques oriented on the recognition of ligand binding area in proteins. In: Roterman-Konieczna I, editor. Identification of ligand binding site and protein-protein interaction area. Dordrecht: Springer, 2013: 55–86.Search in Google Scholar
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