4YKD

Crystal structure of truncated cerebral cavernous malformation 2 C-terminal adaptor domain

4YKD の概要

• エントリーDOI: 10.2210/pdb4ykd/pdb
• 関連するPDBエントリー: 4YKC 4YL6
• 分子名称: Malcavernin (2 entities in total)
• 機能のキーワード: adaptor protein, protein binding
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Cytoplasm : Q9BSQ5
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 11302.81

構造登録者

Ding, J.,Wang, X.,Wang, D.C. (登録日: 2015-03-04, 公開日: 2015-06-03, 最終更新日: 2023-11-08)

主引用文献

Wang, X.,Hou, Y.,Deng, K.,Zhang, Y.,Wang, D.C.,Ding, J.
Structural Insights into the Molecular Recognition between Cerebral Cavernous Malformation 2 and Mitogen-Activated Protein Kinase Kinase Kinase 3
Structure, 23:1087-1096, 2015

PubMed Abstract: Cerebral cavernous malformation 2 (CCM2) functions as an adaptor protein implicated in various biological processes. By interacting with the mitogen-activated protein kinase MEKK3, CCM2 either mediates the activation of MEKK3 signaling in response to osmotic stress or negatively regulates MEKK3 signaling, which is important for normal cardiovascular development. However, the molecular basis governing CCM2-MEKK3 interaction is largely unknown. Here we report the crystal structure of the CCM2 C-terminal part (CCM2ct) containing both the five-helix domain (CCM2cts) and the following C-terminal tail. The end of the C-terminal tail forms an isolated helix, which interacts intramolecularly with CCM2cts. By biochemical studies we identified the N-terminal amphiphilic helix of MEKK3 (MEKK3-nhelix) as the essential structural element for CCM2ct binding. We further determined the crystal structure of CCM2cts-MEKK3-nhelix complex, in which MEKK3-nhelix binds to the same site of CCM2cts for CCM2ct intramolecular interaction. These findings build a structural framework for understanding CCM2ct-MEKK3 molecular recognition.

PubMed: 25982527
DOI: 10.1016/j.str.2015.04.003

実験手法

X-RAY DIFFRACTION (1.932 Å)