钙调神经磷酸酶的盐桥对于传递钙调神经磷酸酶结合蛋白（CNB）与钙调神经磷酸酶 A 亚基（CNA）结合的效应至关重要。

The salt bridge of calcineurin is important for transferring the effect of CNB binding to CNA.

作者信息

Hou Qiang, Yi Xiang, Jiang Guohua, Wei Qun

机构信息

Department of Biochemistry and Molecular Biology, Beijing Normal University, Beijing Key Laboratory, Beijing 100875, PR China.

出版信息

FEBS Lett. 2004 Nov 5;577(1-2):294-8. doi: 10.1016/j.febslet.2004.10.002.

DOI:10.1016/j.febslet.2004.10.002

PMID:15527802

Abstract

Calcineurin (CN) is a heterodimer consisting of a catalytic subunit (CNA) and a regulatory subunit (CNB). The crystal structure shows that three residues or regions of CNA are mainly responsible for the interaction with CNB: the CNB binding helix (BBH), the N-terminus, and Glu53 that forms a salt bridge with Lys134 of CNB. In this report, we try to find the role that the salt bridge plays in the interaction between CNA and CNB. We found that mutation of Glu53 greatly reduced its responsiveness to CNB in the phosphatase assay and also that mutation of Lys134 of CNB affected its ability to activate the phosphatase activity of CNA. Structural analysis showed that disruption of the salt bridge affected the compact association of CNA and CNB. Thus, the salt bridge appears to help to stabilize CN and transfer the effects of CNB binding to CNA to activate its phosphatase activity.

摘要

钙调神经磷酸酶（CN）是一种由催化亚基（CNA）和调节亚基（CNB）组成的异源二聚体。晶体结构表明，CNA的三个残基或区域主要负责与CNB的相互作用：CNB结合螺旋（BBH）、N端以及与CNB的Lys134形成盐桥的Glu53。在本报告中，我们试图探究盐桥在CNA与CNB相互作用中所起的作用。我们发现，Glu53的突变在磷酸酶测定中极大地降低了其对CNB的反应性，并且CNB的Lys134突变影响了其激活CNA磷酸酶活性的能力。结构分析表明，盐桥的破坏影响了CNA与CNB的紧密结合。因此，盐桥似乎有助于稳定CN，并将CNB结合对CNA的影响传递以激活其磷酸酶活性。