Allosteric activation of SENP1 by SUMO1 β-grasp domain involves a dock-and-coalesce mechanism
Abstract
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.
Article and author information
Author details
Funding
National Institutes of Health (GM058187)
- Huan-Xiang Zhou
National Institutes of Health (GM118091)
- Huan-Xiang Zhou
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2016, Guo & Zhou
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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