Journal
STRUCTURE
Volume 31, Issue 4, Pages -Publisher
CELL PRESS
DOI: 10.1016/j.str.2023.02.002
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Protein kinases of the DMPK family are crucial for actomyosin contractility. MRCK1, a DMPK kinase, is necessary for myosin activation, which leads to cortical tension, apical constriction, and early gastrulation. This study provides insights into the structure, conformation, and membrane-binding properties of Caenorhabditis elegans MRCK1. It reveals a homodimer structure of MRCK1, consisting of N-terminal kinase domains, a coiled coil, and a C-terminal module with C1, PH, and CNH domains. The study also investigates the interaction between the CRIB motif and Cdc42 and suggests that the coiled-coil domain may function as a molecular ruler for kinase activity.
Protein kinases of the dystonia myotonica protein kinase (DMPK) family are critical regulators of actomyosin contractility in cells. The DMPK kinase MRCK1 is required for the activation of myosin, leading to the develop-ment of cortical tension, apical constriction, and early gastrulation. Here, we present the structure, conforma-tion, and membrane-binding properties of Caenorhabditis elegans MRCK1. MRCK1 forms a homodimer with N-terminal kinase domains, a parallel coiled coil of 55 nm, and a C-terminal tripartite module of C1, pleckstrin homology (PH), and citron homology (CNH) domains. We report the high-resolution structure of the membrane -binding C1-PH-CNH module of MRCK1 and, using high-throughput and conventional liposome-binding assays, determine its binding to specific phospholipids. We further characterize the interaction of the C -termi-nal CRIB motif with Cdc42. The length of the coiled-coil domain of DMPK kinases is remarkably conserved over millions of years of evolution, suggesting that they may function as molecular rulers to position kinase activity at a fixed distance from the membrane.
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