Crystal structures of human CaMKIα reveal insights into the regulation mechanism of CaMKI.
Human calcium/calmodulin-dependent protein kinase I (CaMKI) plays pivotal roles in the nervous system. The activity of human CaMKI is regulated by a regulatory region including an autoinhibitory segment and a CaM-binding segment. We report here four structures of three CaMKIα truncates in apo form a...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3447817?pdf=render |
| _version_ | 1811336789620686848 |
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| author | Manwu Zha Chen Zhong Ying Ou Li Han Jianchuan Wang Jianping Ding |
| author_facet | Manwu Zha Chen Zhong Ying Ou Li Han Jianchuan Wang Jianping Ding |
| author_sort | Manwu Zha |
| collection | DOAJ |
| description | Human calcium/calmodulin-dependent protein kinase I (CaMKI) plays pivotal roles in the nervous system. The activity of human CaMKI is regulated by a regulatory region including an autoinhibitory segment and a CaM-binding segment. We report here four structures of three CaMKIα truncates in apo form and in complexes with ATP. In an apo, autoinhibited structure, the activation segment adopts a unique helical conformation which together with the autoinhibitory segment constrains helices αC and αD in inactive conformations, sequesters Thr177 from being phosphorylated, and occludes the substrate-binding site. In an ATP-bound, inactive structure, the activation segment is largely disordered and the CaM-binding segment protrudes out ready for CaM binding. In an ATP-bound, active structure, the regulatory region is dissociated from the catalytic core and the catalytic site assumes an active conformation. Detailed structural analyses reveal the interplay of the regulatory region, the activation segment, and the nucleotide-binding site in the regulation of CaMKI. |
| first_indexed | 2024-04-13T17:44:40Z |
| format | Article |
| id | doaj.art-e13ae3e8044e4dfb95a368d322795d02 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-13T17:44:40Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
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| spelling | doaj.art-e13ae3e8044e4dfb95a368d322795d022022-12-22T02:37:02ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0179e4482810.1371/journal.pone.0044828Crystal structures of human CaMKIα reveal insights into the regulation mechanism of CaMKI.Manwu ZhaChen ZhongYing OuLi HanJianchuan WangJianping DingHuman calcium/calmodulin-dependent protein kinase I (CaMKI) plays pivotal roles in the nervous system. The activity of human CaMKI is regulated by a regulatory region including an autoinhibitory segment and a CaM-binding segment. We report here four structures of three CaMKIα truncates in apo form and in complexes with ATP. In an apo, autoinhibited structure, the activation segment adopts a unique helical conformation which together with the autoinhibitory segment constrains helices αC and αD in inactive conformations, sequesters Thr177 from being phosphorylated, and occludes the substrate-binding site. In an ATP-bound, inactive structure, the activation segment is largely disordered and the CaM-binding segment protrudes out ready for CaM binding. In an ATP-bound, active structure, the regulatory region is dissociated from the catalytic core and the catalytic site assumes an active conformation. Detailed structural analyses reveal the interplay of the regulatory region, the activation segment, and the nucleotide-binding site in the regulation of CaMKI.http://europepmc.org/articles/PMC3447817?pdf=render |
| spellingShingle | Manwu Zha Chen Zhong Ying Ou Li Han Jianchuan Wang Jianping Ding Crystal structures of human CaMKIα reveal insights into the regulation mechanism of CaMKI. PLoS ONE |
| title | Crystal structures of human CaMKIα reveal insights into the regulation mechanism of CaMKI. |
| title_full | Crystal structures of human CaMKIα reveal insights into the regulation mechanism of CaMKI. |
| title_fullStr | Crystal structures of human CaMKIα reveal insights into the regulation mechanism of CaMKI. |
| title_full_unstemmed | Crystal structures of human CaMKIα reveal insights into the regulation mechanism of CaMKI. |
| title_short | Crystal structures of human CaMKIα reveal insights into the regulation mechanism of CaMKI. |
| title_sort | crystal structures of human camkiα reveal insights into the regulation mechanism of camki |
| url | http://europepmc.org/articles/PMC3447817?pdf=render |
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