Role of promiscuous binding and intrinsic disorder in protein interactions

12:00 noon, October 27, Tuesday, 2009, ENGR 4201

Speaker

Anna Panchenko
Associate Investigator
NCBI, NIH

Abstract

Cellular processes are highly interconnected and many proteins are shared in different pathways. Some of these shared proteins or protein families may interact with diverse partners using the same interface regions. Analysis of such regions is essential for understanding the mechanisms of specific molecular recognition of multiple diverse partners. We find that only 5% of protein families in the structure database have multibinding interfaces, and they do not show any higher sequence conservation compared with the background interface sites. We highlight several important functional mechanisms utilized by multibinding families. Promiscuous interactions can also be studied by using our recently developed IBIS server (Inferred Biomolecular Interaction Server, http://www.ncbi.nlm.nih.gov/Structure/ibis/ibis.html) which analyzes and annotates the interaction partners and locations of binding sites in proteins.

It has been suggested that intrinsic disorder contributes to the ability of some proteins to interact with multiple partners as folding of disordered proteins into ordered structures may occur upon binding to their specific partners.We performed a large-scale study of intrinsically disordered regions in proteins and protein complexes. In accordance with the conventional view that folding and binding are coupled, in many of our cases the disorder-to-order transition occurs upon complex formation and can be localized to binding interfaces. Moreover, analysis of disorder in protein complexes depicts a significant fraction of intrinsically disordered regions, with up to one third of all residues being disordered. We find that the disorder in homodimers, especially in symmetrical homodimers, is significantly higher than in heterodimers and offer an explanation for this interesting phenomenon. The fascinating diversity of roles of disordered regions in various biological processes and protein oligomeric forms shown in our study is an important subject for future endeavors in this area.

Short Bio

Anna Panchenko received her PhD in biophysics from Moscow State University and subsequently moved to the United States to work on protein molecular dynamics and folding at the University of Illinois at Urbana-Champaign. She subsequently joined the National Center for Biotechnology Information of the National Institutes of Health where she is currently an Associate Investigator. Over time her research on protein folding has motivated the development of methods for protein structure prediction, protein domain classification, and functional annotation. The primary goal of Dr Panchenko's current research is to study the diversity and specificity of protein interactions and understand the main principles of protein binding and the evolution of protein interaction networks. Dr. Panchenko has authored and co-authored more than forty articles and book chapters, served as an editor for a recently published book on protein-protein interactions and for several high-impact journals. She also holds Adjunct Faculty position at Whiting School of Engineering of the Johns Hopkins University.