5HVJ

Crystal structure of LIMK1 D460N mutant in complex with AMP-PNP

5HVJ の概要

• エントリーDOI: 10.2210/pdb5hvj/pdb
• 関連するPDBエントリー: 5HVK
• 分子名称: LIM domain kinase 1, PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER (3 entities in total)
• 機能のキーワード: kinase atp analog actin-remodeling, transferase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 73292.62

構造登録者

Hamill, S.,Boggon, T.J. (登録日: 2016-01-28, 公開日: 2016-05-04, 最終更新日: 2023-09-27)

主引用文献

Hamill, S.,Lou, H.J.,Turk, B.E.,Boggon, T.J.
Structural Basis for Noncanonical Substrate Recognition of Cofilin/ADF Proteins by LIM Kinases.
Mol.Cell, 62:397-408, 2016

PubMed Abstract: Cofilin/actin-depolymerizing factor (ADF) proteins are critical nodes that relay signals from protein kinase cascades to the actin cytoskeleton, in particular through site-specific phosphorylation at residue Ser3. This is important for regulation of the roles of cofilin in severing and stabilizing actin filaments. Consequently, cofilin/ADF Ser3 phosphorylation is tightly controlled as an almost exclusive substrate for LIM kinases. Here we determine the LIMK1:cofilin-1 co-crystal structure. We find an interface that is distinct from canonical kinase-substrate interactions. We validate this previously unobserved mechanism for high-fidelity kinase-substrate recognition by in vitro kinase assays, examination of cofilin phosphorylation in mammalian cells, and functional analysis in S. cerevisiae. The interface is conserved across all LIM kinases. Remarkably, we also observe both pre- and postphosphotransfer states in the same crystal lattice. This study therefore provides a molecular understanding of how kinase-substrate recognition acts as a gatekeeper to regulate actin cytoskeletal dynamics.

PubMed: 27153537
DOI: 10.1016/j.molcel.2016.04.001

実験手法

X-RAY DIFFRACTION (2.2 Å)