Three-Dimensional Structures of Membrane Proteins from Genomic Sequencing
Condensed Matter journal club
Three-Dimensional Structures of Membrane Proteins from Genomic Sequencing
- Event time: 11:30am
- Event date: 6th July 2012
- Speaker: Ulrich Zachariae (Formerly School of Physics & Astronomy, University of Edinburgh)
- Location: Room 2511, James Clerk Maxwell Building (JCMB) James Clerk Maxwell Building Peter Guthrie Tait Road Edinburgh EH9 3FD GB
Event details
Abstract
We show that amino acid covariation in proteins, extracted from the evolutionary sequence record, can be used to fold transmembrane proteins. We use this technique to predict previously unknown 3D structures for 11 transmembrane proteins (with up to 14 helices) from their sequences alone. The prediction method (EVfold_membrane) applies a maximum entropy approach to infer evolutionary covariation in pairs of sequence positions within a protein family and then generates all-atom models with the derived pairwise distance constraints. We benchmark the approach with blinded de novo computation of known transmembrane protein structures from 23 families, demonstrating unprecedented accuracy of the method for large transmembrane proteins. We show how the method can predict oligomerization, functional sites, and conformational changes in transmembrane proteins. With the rapid rise in large-scale sequencing, more accurate and more comprehensive information on evolutionary constraints can be decoded from genetic variation, greatly expanding the repertoire of transmembrane proteins amenable to modeling by this method.Cell 149 Pages 1-15 (2012)
pdf version of paper
Authors
Thomas A. Hopf, Lucy J. Colwell, Robert Sheridan, Burkhard Rost, Chris Sander, Debora S. Marks
About Condensed Matter journal club
Given the diversity of research in the CM group, chosen topics vary widely. We tend to stick to high-impact journals - Nature, Science, PNAS and PRL have been popular - but this is not prescriptive..