6C9D

Crystal structure of KA1-autoinhibited MARK1 kinase

6C9D の概要

• エントリーDOI: 10.2210/pdb6c9d/pdb
• 分子名称: Serine/threonine-protein kinase MARK1,Serine/threonine-protein kinase MARK1 (2 entities in total)
• 機能のキーワード: kinase, camkl, ka1 domain, autoinhibition, transferase
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 105873.43

構造登録者

Emptage, R.P.,Marmorstein, R. (登録日: 2018-01-26, 公開日: 2018-07-11, 最終更新日: 2023-10-04)

主引用文献

Emptage, R.P.,Lemmon, M.A.,Ferguson, K.M.,Marmorstein, R.
Structural Basis for MARK1 Kinase Autoinhibition by Its KA1 Domain.
Structure, 26:1137-, 2018

PubMed Abstract: The kinase associated-1 (KA1) domain is found at the C-terminus of multiple Ser/Thr protein kinases from yeast to humans, and has been assigned autoinhibitory, membrane-binding, and substrate-targeting roles. Here, we report the crystal structure of the MARK1 kinase/UBA domain bound to its autoinhibitory KA1 domain, revealing an unexpected interface at the αD helix and contacts with both the N- and C-lobes of the kinase domain. We confirm the binding interface location in kinetic studies of variants mutated on the kinase domain surface. Together with other MARK kinase structures, the data implicate that the KA1 domain blocks peptide substrate binding. The structure highlights the kinase-specific autoinhibitory binding modes of different KA1 domains, and provides potential new avenues by which to intervene therapeutically in Alzheimer's disease and cancers in which MARK1 or related kinases are implicated.

PubMed: 30099988
DOI: 10.1016/j.str.2018.05.008

実験手法

X-RAY DIFFRACTION (2.499 Å)