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Allosteric activation of SENP1 by SUMO1 β-grasp domain involves a dock-and-coalesce mechanism.

Title: Allosteric activation of SENP1 by SUMO1 β-grasp domain involves a dock-and-coalesce mechanism.
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Name(s): Guo, Jingjing, author
Zhou, Huan-Xiang, author
Type of Resource: text
Genre: Journal Article
Text
Date Issued: 2016-08-31
Physical Form: computer
online resource
Extent: 1 online resource
Language(s): English
Abstract/Description: Small ubiquitin-related modifiers (SUMOs) are conjugated to proteins to regulate a variety of cellular processes. SENPs are cysteine proteases with a catalytic center located within a channel between two subdomains that catalyzes SUMO C-terminal cleavage for processing of SUMO precursors and de-SUMOylation of target proteins. The β-grasp domain of SUMOs binds to an exosite cleft, and allosterically activates SENPs via an unknown mechanism. Our molecular dynamics simulations showed that binding of the β-grasp domain induces significant conformational and dynamic changes in SENP1, including widening of the exosite cleft and quenching of nanosecond dynamics in all but a distal region. A dock-and-coalesce mechanism emerges for SENP-catalyzed SUMO cleavage: the wedging of the β-grasp domain enables the docking of the proximal portion of the C-terminus and the strengthened cross-channel motional coupling initiates inter-subdomain correlated motions to allow for the distal portion to coalesce around the catalytic center.
Identifier: FSU_pmch_27576863 (IID), 10.7554/eLife.18249 (DOI), PMC5030089 (PMCID), 27576863 (RID), 27576863 (EID)
Keywords: SUMOylation, Allosteric activation, Biophysics, Dock-and-coalesce, Human, Protein dynamics, Structural biology
Grant Number: R01 GM058187, R35 GM118091
Publication Note: This NIH-funded author manuscript originally appeared in PubMed Central at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5030089.
Subject(s): Allosteric Regulation
Cysteine Endopeptidases/chemistry
Cysteine Endopeptidases/metabolism
Humans
Models, Biological
Models, Molecular
Molecular Dynamics Simulation
Protein Binding
Protein Conformation
SUMO-1 Protein/chemistry
SUMO-1 Protein/metabolism
Persistent Link to This Record: http://purl.flvc.org/fsu/fd/FSU_pmch_27576863
Owner Institution: FSU
Is Part Of: eLife.
2050-084X
Issue: vol. 5

Choose the citation style.
Guo, J., & Zhou, H. -X. (2016). Allosteric activation of SENP1 by SUMO1 β-grasp domain involves a dock-and-coalesce mechanism. Elife. Retrieved from http://purl.flvc.org/fsu/fd/FSU_pmch_27576863