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 development of cortical tension, apical constriction, and early gastrulation. Here, we present the structure, conformation, 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-terminal 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.

肌张力障碍蛋白激酶 (DMPK) 家族的蛋白激酶是细胞中肌动球蛋白收缩性的关键调节剂。DMPK 激酶 MRCK1 是激活肌球蛋白所必需的，从而导致皮质张力、顶端收缩和早期原肠胚形成的发展。在这里，我们展示了秀丽隐杆线虫的结构、构象和膜结合特性MRCK1。MRCK1 形成一个同型二聚体，具有 N 末端激酶结构域、55 nm 的平行盘绕线圈和 C1、pleckstrin 同源 (PH) 和 citron 同源 (CNH) 结构域的 C 末端三联模块。我们报告了 MRCK1 的膜结合 C1-PH-CNH 模块的高分辨率结构，并使用高通量和常规脂质体结合测定，确定其与特定磷脂的结合。我们进一步描述了 C 端 CRIB 基序与 Cdc42 的相互作用。在数百万年的进化过程中，DMPK 激酶的卷曲螺旋结构域的长度非常保守，这表明它们可能起到分子标尺的作用，将激酶活性定位在距膜的固定距离处。