4GEH

Crystal structure of MST4 dimerization domain complex with PDCD10

4GEH の概要

• エントリーDOI: 10.2210/pdb4geh/pdb
• 分子名称: Programmed cell death protein 10, Serine/threonine-protein kinase MST4 (3 entities in total)
• 機能のキーワード: alpha helix-rich protein, serine/threonine-protein kinase, protein binding, cell proliferation, cell growth, protein binding-transferase complex, protein binding/transferase
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Cytoplasm: Q9BUL8 Q9P289
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 67930.20

構造登録者

Zhang, M.,Shi, Z.B.,Zhou, Z.C. (登録日: 2012-08-02, 公開日: 2013-04-17, 最終更新日: 2024-03-20)

主引用文献

Zhang, M.,Dong, L.,Shi, Z.,Jiao, S.,Zhang, Z.,Zhang, W.,Liu, G.,Chen, C.,Feng, M.,Hao, Q.,Wang, W.,Yin, M.,Zhao, Y.,Zhang, L.,Zhou, Z.
Structural mechanism of CCM3 heterodimerization with GCKIII kinases
Structure, 21:680-688, 2013

PubMed Abstract: 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 flip over 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.

PubMed: 23541896
DOI: 10.1016/j.str.2013.02.015

実験手法

X-RAY DIFFRACTION (1.95 Å)