Met872 是决定代谢型谷氨酸受体 7 与钙调蛋白新型二联体结合的关键残基。

Met872 is the key residue determining the novel binominal binding of metabotropic glutamate receptor 7 to calmodulin.

机构信息

Center for Nano Materials and Technology (CNMT), Japan Advanced Institute of Science and Technology (JAIST), 1-1 Asahidai, Nomi, Ishikawa, 923-1292, Japan.

出版信息

Biochem Biophys Res Commun. 2019 Dec 10;520(3):640-644. doi: 10.1016/j.bbrc.2019.10.053. Epub 2019 Oct 15.

DOI:10.1016/j.bbrc.2019.10.053

PMID:31627896

Abstract

Two mGluR7-derived peptides corresponding to residues 856 to 879 and 856 to 875 are known to bind to Ca-saturated calmodulin (Ca/CaM), and their binding manners are thought to differ. Met872 function is believed as one of the anchor residues for CaM-binding only in the shorter peptide. To uncover the role of Met872 in CaM-binding, we prepared a mutant of the long peptide, mGluR7 (M872A), in which Met872 was replaced with Ala. We used the mutant together with the two peptides to perform NMR-titration experiments to monitor interaction with stable isotope-labeled CaM. Interaction of Ca/CaM with mGluR7 (M872A) caused a spectrum that differed from that of Ca/CaM with the long peptide, suggesting that Met872 of mGluR7 could be involved in CaM-binding even in the long peptide. Analyses of all NMR data suggested that the binding between Ca/CaM and mGluR7 occurs in some conformational equilibrium manner. The unique CaM-binding properties caused by Met872 may be related to mGluR7's function.

摘要

两种源自 mGluR7 的肽段（856 到 879 残基和 856 到 875 残基）已知能与 Ca 饱和的钙调蛋白（Ca/CaM）结合，它们的结合方式被认为不同。Met872 功能被认为是仅在较短肽段中与 CaM 结合的锚定残基之一。为了揭示 Met872 在 CaM 结合中的作用，我们制备了长肽段 mGluR7（M872A）的突变体，其中 Met872 被替换为 Ala。我们使用突变体与两种肽段一起进行 NMR 滴定实验，以监测与稳定同位素标记的 CaM 的相互作用。Ca/CaM 与 mGluR7（M872A）的相互作用产生的谱与 Ca/CaM 与长肽段的谱不同，这表明 mGluR7 的 Met872 即使在长肽段中也可能参与 CaM 结合。对所有 NMR 数据的分析表明，Ca/CaM 与 mGluR7 之间的结合以某种构象平衡方式发生。由 Met872 引起的独特的 CaM 结合特性可能与 mGluR7 的功能有关。