Insights into the energy landscapes of chromosome organization proteins from coevolutionary sequence variation and structural modeling
Year: 2020
Type: article
Abstract: Uncovering mechanisms of protein function is challenging when structural characterization of the functionally relevant states is elusive, for instance for large and flexible proteins which resist crystallization. This is the case for structural maintenance of chromosomes (SMC) proteins and kleisin subunits which are crucial for the segregation of chromosomes during cell division but whose mechanism to organize chromosomes for replication is not known. The two most prominent multisubunit SMC complexes are cohesin and condensin, which form large complexes (more than 650 kDa for condensin) containing long antiparallel coiled coils, making them difficult to study by conventional crystallography or cryoelectron microscopy. Integrative structural biology techniques have arisen in response to these challenges which attempt to solve the puzzle by combining incomplete information from diverse experimental data with computational and theoretical results (1). In PNAS, Krepel et al. (2) use an integrative approach to understanding the mechanism of SMC action which incorporates evolutionary sequence analysis with molecular simulations based on an energy landscape optimized effective potential (AWSEM, associative memory, water-mediated, structure and energy model) along with crystallographic structural information and cross-linking experimental data to map features of the conformational and energy landscapes of SMC proteins. A complete atom-level structural model of several kleisin … [↵][1]1Email: ronlevy{at}temple.edu. [1]: #xref-corresp-1-1
Author: Ronald M. Levy
Institution: Temple University
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W3000505745