Seminario Athi N Naganathan, Indian Institute of Technology Madras (IITM), India: Functional Promiscuity and Protein Dynamics
Marco D'Abramo ha il piacere di invitarvi al seminario:
Functional Promiscuity and Protein Dynamics
di Athi N Naganathan, Indian Institute of Technology Madras (IITM), India
Il seminario avrà luogo venerdì 9 maggio alle ore 11 in Sala Parravano, ed. Cannizzaro (CU014).
Abstract
Paralogous proteins confer enhanced fitness to organisms via complex sequence-conformation codes that shape functional divergence, specialization, or promiscuity. Here, we resolve the underlying mechanism of promiscuous binding versus partial sub-functionalization by studying paralogous Acyl-CoA Binding Proteins (ACBPs) from Plasmodium falciparum. Combining experiments and simulations on two of the paralogs, A16 and A749, we show that minor sequence differences shape nearly every conformational feature. A749 displays a heterogeneous native ensemble, weaker thermodynamic coupling, enhanced fluctuations, and a larger binding-pocket volume, compared to A16. Tryptophan probes signal a graded reduction in the sampling of substates in the holo form, hinting at conformational-selection-like mechanism of binding. They exhibit a spectrum of binding affinities to acyl-CoAs with A749, the more promiscuous and hence the likely ancestor, binding 1000-fold stronger to Lauroyl-CoA. We thus demonstrate how minor differences in long-range coupling and dynamics contribute to the evolution of contrasting functional repertoires in paralogs.
Speaker Summary
Athi N Naganathan is a Professor at the Department of Biotechnology, Indian Institute of Technology Madras (IITM), India. He completed his B.Tech. in Industrial Biotechnology from the Center for Biotechnology (Anna University, India) in 2002 and PhD in Biochemistry from the University of Maryland, College Park, USA in 2007. Following this, he was a Juan de la Cierva post-doctoral fellow at the Barcelona Supercomputing Center, Spain. His Protein Biophysics Lab @IITM has been employing an interdisciplinary approach since 2012 using experimental spectroscopic measurements, functional studies, simulations and theoretical modeling to understand and manipulate the basic energetic and entropic factors governing the folding of proteins, with implications in protein design and engineering. He has authored >80 international peer-reviewed research articles (https://pbl.biotech.iitm.ac.in). He is also a recipient of the JSPS Invitational Fellowship for Research in Japan (2019), INSA Medal for Young Scientists (2015), Wellcome Trust/DBT India Alliance Intermediate Fellowship (2015) and the Innovative Young Biotechnologist Award (IYBA 2012, DBT).