3L8J

Crystal structure of CCM3, a cerebral cavernous malformation protein critical for vascular integrity

3L8J の概要

• エントリーDOI: 10.2210/pdb3l8j/pdb
• 分子名称: Programmed cell death protein 10 (1 entity in total)
• 機能のキーワード: cerebral cavernous malformation, fat domain, dimerization, protein binding
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm: Q9BUL8
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 23376.99

構造登録者

Li, X.,Zhang, R.,Zhang, H.,He, Y.,Ji, W.,Min, W.,Boggon, T.J. (登録日: 2009-12-31, 公開日: 2010-05-19, 最終更新日: 2023-09-06)

主引用文献

Li, X.,Zhang, R.,Zhang, H.,He, Y.,Ji, W.,Min, W.,Boggon, T.J.
Crystal structure of CCM3, a cerebral cavernous malformation protein critical for vascular integrity.
J.Biol.Chem., 285:24099-24107, 2010

PubMed Abstract: CCM3 mutations are associated with cerebral cavernous malformation (CCM), a disease affecting 0.1-0.5% of the human population. CCM3 (PDCD10, TFAR15) is thought to form a CCM complex with CCM1 and CCM2; however, the molecular basis for these interactions is not known. We have determined the 2.5 A crystal structure of CCM3. This structure shows an all alpha-helical protein containing two domains, an N-terminal dimerization domain with a fold not previously observed, and a C-terminal focal adhesion targeting (FAT)-homology domain. We show that CCM3 binds CCM2 via this FAT-homology domain and that mutation of a highly conserved FAK-like hydrophobic pocket (HP1) abrogates CCM3-CCM2 interaction. This CCM3 FAT-homology domain also interacts with paxillin LD motifs using the same surface, and partial CCM3 co-localization with paxillin in cells is lost on HP1 mutation. Disease-related CCM3 truncations affect the FAT-homology domain suggesting a role for the FAT-homology domain in the etiology of CCM.

PubMed: 20489202
DOI: 10.1074/jbc.M110.128470

実験手法

X-RAY DIFFRACTION (3.05 Å)