Allosteric activation of SENP1 by SUMO1 β-grasp domain involves a dock-and-coalesce mechanism
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-SUMO...
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2016-08-01
|
| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/18249 |
| _version_ | 1811235849978773504 |
|---|---|
| author | Jingjing Guo Huan-Xiang Zhou |
| author_facet | Jingjing Guo Huan-Xiang Zhou |
| author_sort | Jingjing Guo |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-12T11:59:04Z |
| format | Article |
| id | doaj.art-91343e31f9974aaeaa00e12166bf9232 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T11:59:04Z |
| publishDate | 2016-08-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-91343e31f9974aaeaa00e12166bf92322022-12-22T03:33:55ZengeLife Sciences Publications LtdeLife2050-084X2016-08-01510.7554/eLife.18249Allosteric activation of SENP1 by SUMO1 β-grasp domain involves a dock-and-coalesce mechanismJingjing Guo0Huan-Xiang Zhou1https://orcid.org/0000-0001-9020-0302Henan Engineering Research Center of Chiral Hydroxyl Pharmaceuticals, School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang, ChinaDepartment of Physics, Institute of Molecular Biophysics, Florida State University, Tallahassee, United StatesSmall 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.https://elifesciences.org/articles/18249allosteric activationSUMOylationprotein dynamicsdock-and-coalesce |
| spellingShingle | Jingjing Guo Huan-Xiang Zhou Allosteric activation of SENP1 by SUMO1 β-grasp domain involves a dock-and-coalesce mechanism eLife allosteric activation SUMOylation protein dynamics dock-and-coalesce |
| title | Allosteric activation of SENP1 by SUMO1 β-grasp domain involves a dock-and-coalesce mechanism |
| title_full | Allosteric activation of SENP1 by SUMO1 β-grasp domain involves a dock-and-coalesce mechanism |
| title_fullStr | Allosteric activation of SENP1 by SUMO1 β-grasp domain involves a dock-and-coalesce mechanism |
| title_full_unstemmed | Allosteric activation of SENP1 by SUMO1 β-grasp domain involves a dock-and-coalesce mechanism |
| title_short | Allosteric activation of SENP1 by SUMO1 β-grasp domain involves a dock-and-coalesce mechanism |
| title_sort | allosteric activation of senp1 by sumo1 β grasp domain involves a dock and coalesce mechanism |
| topic | allosteric activation SUMOylation protein dynamics dock-and-coalesce |
| url | https://elifesciences.org/articles/18249 |
| work_keys_str_mv | AT jingjingguo allostericactivationofsenp1bysumo1bgraspdomaininvolvesadockandcoalescemechanism AT huanxiangzhou allostericactivationofsenp1bysumo1bgraspdomaininvolvesadockandcoalescemechanism |