Please use this identifier to cite or link to this item: http://hdl.handle.net/2381/37590
Title: Structural Insights into Separase Architecture and Substrate Recognition through Computational Modelling of Caspase-Like and Death Domains.
Authors: Winter, Anja
Schmid, Ralf
Bayliss, Richard
First Published: 29-Oct-2015
Publisher: Public Library of Science
Citation: PLoS Computational Biology, 2015, 11 (10), pp. e1004548
Abstract: Separases are large proteins that mediate sister chromatid disjunction in all eukaryotes. They belong to clan CD of cysteine peptidases and contain a well-conserved C-terminal catalytic protease domain similar to caspases and gingipains. However, unlike other well-characterized groups of clan CD peptidases, there are no high-resolution structures of separases and the details of their regulation and substrate recognition are poorly understood. Here we undertook an in-depth bioinformatical analysis of separases from different species with respect to their similarity in amino acid sequence and protein fold in comparison to caspases, MALT-1 proteins (mucosa-associated lymphoidtissue lymphoma translocation protein 1) and gingipain-R. A comparative model of the single C-terminal caspase-like domain in separase from C. elegans suggests similar binding modes of substrate peptides between these protein subfamilies, and enables differences in substrate specificity of separase proteins to be rationalised. We also modelled a newly identified putative death domain, located N-terminal to the caspase-like domain. The surface features of this domain identify potential sites of protein-protein interactions. Notably, we identified a novel conserved region with the consensus sequence WWxxRxxLD predicted to be exposed on the surface of the death domain, which we termed the WR motif. We envisage that findings from our study will guide structural and functional studies of this important protein family.
DOI Link: 10.1371/journal.pcbi.1004548
ISSN: 1553-734X
eISSN: 1553-7358
Links: http://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1004548
http://hdl.handle.net/2381/37590
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright: © 2015 Winter et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Appears in Collections:Published Articles, Dept. of Molecular and Cell Biology



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