Coevolutionary constraints in the sequence-space of macromolecular complexes reflect their self-assembly pathways.
Is the order in which biomolecular subunits self-assemble into functional macromolecular complexes imprinted in their sequence-space? Here, we demonstrate that the temporal order of macromolecular complex self-assembly can be efficiently captured using the landscape of residue-level coevolutionary constraints. This predictive power of coevolutionary constraints is irrespective of the structural, functional, and phylogenetic classification of the complex and of the stoichiometry and quaternary arrangement of the constituent monomers. Combining this result with a number of structural attributes estimated from the crystal structure data, we find indications that stronger coevolutionary constraints at interfaces formed early in the assembly hierarchy probably promotes coordinated fixation of mutations that leads to high-affinity binding with higher surface area, increased surface complementarity and elevated number of molecular contacts, compared to those that form late in the assembly. Proteins 2017; 85:1183-1189. © 2017 Wiley Periodicals, Inc.
Department of Biophysics, Molecular Biology and Bioinformatics, University of Calcutta, Kolkata, West Bengal, India.|Center of Excellence in Systems Biology and Biomedical Engineering (TEQIP Phase-II), University of Calcutta, Kolkata, West Bengal, India.
Saurav
S
Mallik
Department of Biophysics, Molecular Biology and Bioinformatics, University of Calcutta, Kolkata, West Bengal, India.|Center of Excellence in Systems Biology and Biomedical Engineering (TEQIP Phase-II), University of Calcutta, Kolkata, West Bengal, India.
Sudip
0000-0003-1235-2540
S
Kundu
D001419:Bacteria / Q000737:chemistry; D066264:Datasets as Topic; D019143:Evolution, Molecular; D008958:Models, Molecular; D012275:Oryza / Q000737:chemistry; D000072417:Protein Domains; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D021122:Protein Subunits / Q000737:chemistry*; D011506:Proteins / Q000737:chemistry*; D013816:Thermodynamics; D013822:Thermoplasma / Q000737:chemistry
D021122:Protein Subunits; D011506:Proteins
coevolution; macromolecular complex; protein-RNA interaction; protein-protein interaction; self-assembly pathway