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Evolutionary and structural analyses of heterodimeric proteins composed of subunits with same fold

Sudha, Govindarajan and Naveenkumar, Nagarajan and Srinivasan, Narayanaswamy (2015) Evolutionary and structural analyses of heterodimeric proteins composed of subunits with same fold. In: PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS, 83 (10). pp. 1766-1786.

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Official URL: http://dx.doi.org/10.1002/prot.24849


Heterodimeric proteins with homologous subunits of same fold are involved in various biological processes. The objective of this study is to understand the evolution of structural and functional features of such heterodimers. Using a non-redundant dataset of 70 such heterodimers of known 3D structure and an independent dataset of 173 heterodimers from yeast, we note that the mean sequence identity between interacting homologous subunits is only 23-24% suggesting that, generally, highly diverged paralogues assemble to form such a heterodimer. We also note that the functional roles of interacting subunits/domains are generally quite different. This suggests that, though the interacting subunits/domains are homologous, the high evolutionary divergence characterize their high functional divergence which contributes to a gross function for the heterodimer considered as a whole. The inverse relationship between sequence identity and RMSD of interacting homologues in heterodimers is not followed. We also addressed the question of formation of homodimers of the subunits of heterodimers by generating models of fictitious homodimers on the basis of the 3D structures of the heterodimers. Interaction energies associated with these homodimers suggests that, in overwhelming majority of the cases, such homodimers are unlikely to be stable. Majority of the homologues of heterodimers of known structures form heterodimers (51.8%) and a small proportion (14.6%) form homodimers. Comparison of 3D structures of heterodimers with homologous homodimers suggests that interfacial nature of residues is not well conserved. In over 90% of the cases we note that the interacting subunits of heterodimers are co-localized in the cell. Proteins 2015; 83:1766-1786. (c) 2015 Wiley Periodicals, Inc.

Item Type: Journal Article
Additional Information: Copy right for this article belongs to the WILEY-BLACKWELL, 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
Keywords: heterodimers; interacting paralogues; protein function; protein interactions; homodimers; homologous proteins; oligomeric proteins; protein-protein complexes
Department/Centre: Division of Biological Sciences > Molecular Biophysics Unit
Date Deposited: 15 Oct 2015 06:08
Last Modified: 15 Oct 2015 06:08
URI: http://eprints.iisc.ac.in/id/eprint/52547

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