Vijayakumar Gosu
ABSTRACT
Interleukin-1 receptor-associated kinases (IRAKs) are important in TIR-mediated signal transduction. Although IRAK proteins are structurally similar, recent biochemical studies have shown that each IRAK member plays a non-redundant role in TLR/IL-1R signaling. In addition insects have 1 IRAK homolog, Pelle, which is related to the vertebrate IRAK members. We have carried out the sequence based phylogenetic analysis, to understand the molecular evolution of IRAK members and the relation of vertebrate IRAK members with insect homolog. Our study on available IRAK sequences suggested that gene duplication events have occurred in the lineage leading to vertebrates and Tube protein from insects is a homolog of IRAK4 unlike anticipated protein Pelle. Furthermore, our functional analysis suggests that the potential divergence sites have been constrained by strong purifying selection among IRAK members. 3D protein structures revealed some of the unique features of the DD and KD shared by all the IRAK members. Additionally our NMA analysis predicted the domain motions in the KD. This study highlighted the molecular evolution, functional divergence and structural features of the IRAK subfamily that may provide a starting point for further experimental investigations.
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Index Terms
- Phylogenetic and functional divergence analysis of vertebrate IRAK family members
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