TY - JOUR TI - Allosteric activation of SENP1 by SUMO1 β-grasp domain involves a dock-and-coalesce mechanism AU - Guo, Jingjing AU - Zhou, Huan-Xiang A2 - Dötsch, Volker VL - 5 PY - 2016 DA - 2016/08/31 SP - e18249 C1 - eLife 2016;5:e18249 DO - 10.7554/eLife.18249 UR - https://doi.org/10.7554/eLife.18249 AB - 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. KW - allosteric activation KW - SUMOylation KW - protein dynamics KW - dock-and-coalesce JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -