5HVK

Crystal structure of LIMK1 mutant D460N in complex with full-length cofilin-1

Summary for 5HVK

• Entry DOI: 10.2210/pdb5hvk/pdb
• Related: 5HVJ
• Descriptor: LIM domain kinase 1, Cofilin-1, PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER, ... (5 entities in total)
• Functional Keywords: kinase substrate actin-remodeling, transferase
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 4
• Total formula weight: 110950.09

Authors

Hamill, S.,Boggon, T.J. (deposition date: 2016-01-28, release date: 2016-05-04, Last modification date: 2024-10-23)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (3.5 Å)