Abstract：
:Gene duplication is a common evolutionary process that leads to the expansion and functional diversification of protein subfamilies. The evolutionary events that cause paralogous proteins to bind different protein ligands (functionally diverged interfaces) are investigated and compared to paralogous proteins that bind the same protein ligand (functionally preserved interfaces). We find that functionally diverged interfaces possess more subfamily-specific residues than functionally preserved interfaces. These subfamily-specific residues are usually partially buried at the interface rim and achieve specific binding through optimized hydrogen bond geometries. In addition to optimized hydrogen bond geometries, side-chain modeling experiments suggest that steric effects are also important for binding specificity. Residues that are completely buried at the interface hub are also less conserved in functionally diverged interfaces than in functionally preserved interfaces. Consistent with this finding, hub residues contribute less to free energy of binding in functionally diverged interfaces than in functionally preserved interfaces. Therefore, we propose that protein binding is a delicate balance between binding affinity that primarily occurs at the interface hub and binding specificity that primarily occurs at the interface rim.
journal_name
J Mol Bioljournal_title
Journal of molecular biologyauthors
Aiello D,Caffrey DRdoi
10.1016/j.jmb.2012.06.039subject
Has Abstractpub_date
2012-10-19 00:00:00pages
257-72issue
2eissn
0022-2836issn
1089-8638pii
S0022-2836(12)00551-7journal_volume
423pub_type
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