Biochemistry Research Group, Department of Biological Sciences, University of Calgary, Calgary, Alberta T2N 1N4, Canada.
J Biol Chem. 2012 Aug 3;287(32):26513-27. doi: 10.1074/jbc.M112.373373. Epub 2012 Jun 18.
The L-selectin glycoprotein receptor mediates the initial steps of leukocyte migration into secondary lymphoid organs and sites of inflammation. Following cell activation through the engagement of G-protein-coupled receptors or immunoreceptors, the extracellular domains of L-selectin are rapidly shed, a process negatively controlled via the binding of the ubiquitous eukaryotic calcium-binding protein calmodulin to the cytoplasmic tail of L-selectin. Here we present the solution structure of calcium-calmodulin bound to a peptide encompassing the cytoplasmic tail and part of the transmembrane domain of L-selectin. The structure and accompanying biophysical study highlight the importance of both calcium and the transmembrane segment of L-selectin in the interaction between these two proteins, suggesting that by binding this region, calmodulin regulates in an "inside-out" fashion the ectodomain shedding of the receptor. Our structure provides the first molecular insight into the emerging new role for calmodulin as a transmembrane signaling partner.
L-选择素糖蛋白受体介导白细胞向次级淋巴器官和炎症部位的初始迁移步骤。在通过 G 蛋白偶联受体或免疫受体的细胞激活后，L-选择素的细胞外结构域迅速脱落，该过程通过普遍存在的真核钙结合蛋白钙调蛋白与 L-选择素细胞质尾巴的结合来负调控。在这里，我们展示了钙-钙调蛋白与包含 L-选择素细胞质尾巴和部分跨膜结构域的肽结合的溶液结构。该结构及其伴随的生物物理研究强调了钙和 L-选择素跨膜片段在这两种蛋白质相互作用中的重要性，表明通过结合该区域，钙调蛋白以“内向外”的方式调节受体的胞外结构域脱落。我们的结构首次提供了对钙调蛋白作为跨膜信号伙伴的新兴新作用的分子见解。
