Structural Mechanism of CCM3 Heterodimerization with GCKIII Kinases
文献类型：期刊论文
| 作者 | Zhang, M; Dong, L; Shi, ZB; Jiao, S; Zhang, Z; Zhang, WQ; Liu, GG; Chen, CC; Feng, M; Hao, Q |
| 刊名 | STRUCTURE
 |
| 出版日期 | 2013 |
| 卷号 | 21期号:4页码:680-688 |
| 通讯作者 | Zhang, L (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, State Key Lab Cell Biol, Inst Biochem & Cell Biol, Shanghai 200031, Peoples R China.,rayzhang@sibcb.ac.cn ; zczhou@sibcb.ac.cn |
| 英文摘要 | Mutation of CCM3 causes cerebral cavernous malformations of the vasculature, leading to focal neurological deficits, seizures, and hemorrhagic stroke. CCM3 can heterodimerize with GCKIII kinases (MST3, MST4, and STK25) to regulate cardiovascular development. Here, we provide direct experimental evidence to prove that CCM3 heterodimerizes with GCKIII in a manner structurally resembling the CCM3 homodimerization. Structural comparison revealed the mechanism and critical residues that drive CCM3-GCKIII heterodimerization versus homodimerization. A flexible linker was identified for CCM3, which mediates a large-scale conformational rotation of the FAT domain relative to the dimerization domain. The conformational flipover of FAT domain removes steric locking in the CCM3 homodimer and allows its disassembly and subsequent heterodimerization with GCKIII. CCM3 forms a stable complex with MST4 in vivo to promote cell proliferation and migration synergistically in a manner dependent on MST4 kinase activity. Collectively, our work offers a structural basis for further functional study. |
| 学科主题 | Biochemistry & Molecular Biology; Biophysics; Cell Biology |
| 类目[WOS] | Biochemistry & Molecular Biology ; Biophysics ; Cell Biology |
| 关键词[WOS] | CEREBRAL CAVERNOUS MALFORMATIONS ; IN-FRAME DELETION ; STE20-RELATED KINASE ; RECENT INSIGHTS ; CELL-MIGRATION ; PROTEIN ; MST4 ; MUTATIONS ; APOPTOSIS ; COMPLEX |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000317800100018 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.143/handle/331003/375]  |
| 专题 | 上海生化细胞研究所_上海生科院生化细胞研究所 |
| 推荐引用方式 GB/T 7714 | Zhang, M,Dong, L,Shi, ZB,et al. Structural Mechanism of CCM3 Heterodimerization with GCKIII Kinases[J]. STRUCTURE,2013,21(4):680-688. |
| APA | Zhang, M.,Dong, L.,Shi, ZB.,Jiao, S.,Zhang, Z.,...&Zhou, ZC.(2013).Structural Mechanism of CCM3 Heterodimerization with GCKIII Kinases.STRUCTURE,21(4),680-688. |
| MLA | Zhang, M,et al."Structural Mechanism of CCM3 Heterodimerization with GCKIII Kinases".STRUCTURE 21.4(2013):680-688. |
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