心肌肌钙蛋白C-肌钙蛋白I复合物的核磁共振分析：磷酸化的影响

NMR analysis of cardiac troponin C-troponin I complexes: effects of phosphorylation.

作者信息

Finley N, Abbott M B, Abusamhadneh E, Gaponenko V, Dong W, Gasmi-Seabrook G, Howarth J W, Rance M, Solaro R J, Cheung H C, Rosevear P R

机构信息

Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati, College of Medicine, OH 45267, USA.

出版信息

FEBS Lett. 1999 Jun 18;453(1-2):107-12. doi: 10.1016/s0014-5793(99)00693-6.

DOI:10.1016/s0014-5793(99)00693-6

PMID:10403385

Abstract

Phosphorylation of the cardiac specific amino-terminus of troponin I has been demonstrated to reduce the Ca2+ affinity of the cardiac troponin C regulatory site. Recombinant N-terminal cardiac troponin I proteins, cardiac troponin I(33-80), cardiac troponin I(1-80), cardiac troponin I(1-80)DD and cardiac troponin I(1-80)pp, phosphorylated by protein kinase A, were used to form stable binary complexes with recombinant cardiac troponin C. Cardiac troponin I(1-80)DD, having phosphorylated Ser residues mutated to Asp, provided a stable mimetic of the phosphorylated state. In all complexes, the N-terminal domain of cardiac troponin I primarily makes contact with the C-terminal domain of cardiac troponin C. The nonphosphorylated cardiac specific amino-terminus, cardiac troponin I(1-80), was found to make additional interactions with the N-terminal domain of cardiac troponin C.

摘要

肌钙蛋白I心脏特异性氨基末端的磷酸化已被证明可降低心肌肌钙蛋白C调节位点对Ca2+的亲和力。用蛋白激酶A磷酸化的重组N端心肌肌钙蛋白I蛋白、心肌肌钙蛋白I(33-80)、心肌肌钙蛋白I(1-80)、心肌肌钙蛋白I(1-80)DD和心肌肌钙蛋白I(1-80)pp，用于与重组心肌肌钙蛋白C形成稳定的二元复合物。心肌肌钙蛋白I(1-80)DD的丝氨酸残基磷酸化后突变为天冬氨酸，提供了一种稳定的磷酸化状态模拟物。在所有复合物中，心肌肌钙蛋白I的N端结构域主要与心肌肌钙蛋白C的C端结构域接触。发现非磷酸化的心脏特异性氨基末端，即心肌肌钙蛋白I(1-80)，与心肌肌钙蛋白C的N端结构域有额外的相互作用。