title: Weak conservation of structural features in the interfaces of homologous transient protein-protein complexes.
abstract: Residue types at the interface of protein-protein complexes (PPCs) are known to be reasonably well conserved. However, we show, using a dataset of known 3-D structures of homologous transient PPCs, that the 3-D location of interfacial residues and their interaction patterns are only moderately and poorly conserved, respectively. Another surprising observation is that a residue at the interface that is conserved is not necessarily in the interface in the homolog. Such differences in homologous complexes are manifested by substitution of the residues that are spatially proximal to the conserved residue and structural differences at the interfaces as well as differences in spatial orientations of the interacting proteins. Conservation of interface location and the interaction pattern at the core of the interfaces is higher than at the periphery of the interface patch. Extents of variability of various structural features reported here for homologous transient PPCs are higher than the variation in homologous permanent homomers. Our findings suggest that straightforward extrapolation of interfacial nature and inter-residue interaction patterns from template to target could lead to serious errors in the modeled complex structure. Understanding the evolution of interfaces provides insights to improve comparative modeling of PPC structures.
authors: Molecular Biophysics Unit, Indian Institute of Science, Bangalore, 560012, Karnataka, India.
authors: Govindarajan
authors: G
authors: Sudha
authors: Molecular Biophysics Unit, Indian Institute of Science, Bangalore, 560012, Karnataka, India.
authors: Prashant
authors: P
authors: Singh
authors: Molecular Biophysics Unit, Indian Institute of Science, Bangalore, 560012, Karnataka, India.
authors: Lakshmipuram S
authors: LS
authors: Swapna
authors: Molecular Biophysics Unit, Indian Institute of Science, Bangalore, 560012, Karnataka, India.
authors: Narayanaswamy
authors: N
authors: Srinivasan
mesh_terms: D001665:Binding Sites; D008958:Models, Molecular; D046912:Multiprotein Complexes / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D040681:Structural Homology, Protein; D013499:Surface Properties
chemical_list: D046912:Multiprotein Complexes
keywords: evolution of protein complexes; interfaces of protein complexes; protein-protein interactions; structure of protein complexes; transient protein complexes