6LNM

Crystal structure of CASK-CaMK in complex with Mint1-CID

6LNM の概要

• エントリーDOI: 10.2210/pdb6lnm/pdb
• 分子名称: Peripheral plasma membrane protein CASK, Amyloid-beta A4 precursor protein-binding family A member 1 (3 entities in total)
• 機能のキーワード: cask, lin-2, maguk, mint1, camk, calmodulin-dependent protein kinase, transferase
• 由来する生物種: Rattus norvegicus (Rat); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 135719.86

構造登録者

Cai, Q.,Zhang, M. (登録日: 2019-12-31, 公開日: 2020-04-08, 最終更新日: 2023-11-22)

主引用文献

Wu, X.,Cai, Q.,Chen, Y.,Zhu, S.,Mi, J.,Wang, J.,Zhang, M.
Structural Basis for the High-Affinity Interaction between CASK and Mint1.
Structure, 28:664-673.e3, 2020

PubMed Abstract: CASK forms an evolutionarily conserved tripartite complex with Mint1 and Veli critical for neuronal synaptic transmission and cell polarity. The CASK CaM kinase (CaMK) domain, in addition to interacting with Mint1, can also bind to many different target proteins, although the mechanism governing CASK-CaMK/target interaction selectivity is unclear. Here, we demonstrate that an extended sequence in the N-terminal unstructured region of Mint1 binds to CASK-CaMK with a dissociation constant of ∼7.5 nM. The high-resolution crystal structure of CASK-CaMK in complex with this Mint1 fragment reveals that the C-lobe of CASK-CaMK binds to a short sequence common to known CaMK targets and the N-lobe of CaMK engages an α helix that is unique to Mint1. Biochemical experiments together with structural analysis reveal that the CASK and Mint1 interaction is not regulated by Ca/CaM. The CASK/Mint1 complex structure provides mechanistic explanations for several CASK mutations identified in patients with brain disorders and cancers.

PubMed: 32348748
DOI: 10.1016/j.str.2020.04.001

実験手法

X-RAY DIFFRACTION (2.4 Å)