Structural highlights
Function
COF1_HUMAN Binds to F-actin and exhibits pH-sensitive F-actin depolymerizing activity. Regulates actin cytoskeleton dynamics. Important for normal progress through mitosis and normal cytokinesis. Plays a role in the regulation of cell morphology and cytoskeletal organization.[1] [2]
Publication Abstract from PubMed
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.
Structural Basis for Noncanonical Substrate Recognition of Cofilin/ADF Proteins by LIM Kinases.,Hamill S, Lou HJ, Turk BE, Boggon TJ Mol Cell. 2016 May 5;62(3):397-408. doi: 10.1016/j.molcel.2016.04.001. PMID:27153537[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Gohla A, Birkenfeld J, Bokoch GM. Chronophin, a novel HAD-type serine protein phosphatase, regulates cofilin-dependent actin dynamics. Nat Cell Biol. 2005 Jan;7(1):21-9. Epub 2004 Dec 5. PMID:15580268 doi:10.1038/ncb1201
- ↑ Bai SW, Herrera-Abreu MT, Rohn JL, Racine V, Tajadura V, Suryavanshi N, Bechtel S, Wiemann S, Baum B, Ridley AJ. Identification and characterization of a set of conserved and new regulators of cytoskeletal organization, cell morphology and migration. BMC Biol. 2011 Aug 11;9:54. doi: 10.1186/1741-7007-9-54. PMID:21834987 doi:10.1186/1741-7007-9-54
- ↑ Hamill S, Lou HJ, Turk BE, Boggon TJ. Structural Basis for Noncanonical Substrate Recognition of Cofilin/ADF Proteins by LIM Kinases. Mol Cell. 2016 May 5;62(3):397-408. doi: 10.1016/j.molcel.2016.04.001. PMID:27153537 doi:http://dx.doi.org/10.1016/j.molcel.2016.04.001
