title: Specificity and stability of transient protein-protein interactions.
abstract: Remarkable features that are achieved in a protein-protein complex to precise levels are stability and specificity. Deviation from the normal levels of specificity and stability, which is often caused by mutations, could result in disease conditions. Chemical nature, 3-D arrangement and dynamics of interface residues code for both specificity and stability. This article reviews roles of interfacial residues in transient protein-protein complexes. It is proposed that aside from hotspot residues conferring stability to the complex, a small set of 'rigid' residues at the interface that maintain conformation between complexed and uncomplexed forms, play a major role in conferring specificity. Exceptionally, 'super hotspot' residues, which confer both stability and specificity, are attractive sites for interaction with small molecule inhibitors.
authors.affiliation: Molecular Biophysics Unit, Indian Institute of Science, Bangalore 560012, India.
authors.forename: Sneha
authors.initials: S
authors.lastname: Vishwanath
authors.affiliation: National Centre for Biological Sciences, TIFR, UAS-GKVK Campus, Bellary road, Bangalore 560065, India; SASTRA Deemed University, Tirumalai Samudram, Thanjavur 613402, India.
authors.forename: Anshul
authors.initials: A
authors.lastname: Sukhwal
authors.affiliation: National Centre for Biological Sciences, TIFR, UAS-GKVK Campus, Bellary road, Bangalore 560065, India.
authors.forename: Ramanathan
authors.initials: R
authors.lastname: Sowdhamini
authors.affiliation: Molecular Biophysics Unit, Indian Institute of Science, Bangalore 560012, India. Electronic address: ns@mbu.iisc.ernet.in.
authors.forename: Narayanaswamy
authors.initials: N
authors.lastname: Srinivasan
mesh_terms: D006801:Humans; D011485:Protein Binding; D025941:Protein Interaction Mapping / Q000379:methods*; D055550:Protein Stability; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*; D013379:Substrate Specificity
chemical_list: D011506:Proteins