期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2020
卷号：117
期号：31
页码：18448-18458
DOI：10.1073/pnas.2006027117
出版社：The National Academy of Sciences of the United States of America
摘要：Under physiological conditions, most Ca 2 -ATPase (SERCA) molecules bind ATP before binding the Ca 2 transported. SERCA has a high affinity for ATP even in the absence of Ca 2 , and ATP accelerates Ca 2 binding at pH values lower than 7, where SERCA is in the E2 state with low-affinity Ca 2 -binding sites. Here we describe the crystal structure of SERCA2a, the isoform predominant in cardiac muscle, in the E2·ATP state at 3.0-Å resolution. In the crystal structure, the arrangement of the cytoplasmic domains is distinctly different from that in canonical E2. The A-domain now takes an E1 position, and the N-domain occupies exactly the same position as that in the E1·ATP·2Ca 2 state relative to the P-domain. As a result, ATP is properly delivered to the phosphorylation site. Yet phosphoryl transfer never takes place without the filling of the two transmembrane Ca 2 -binding sites. The present crystal structure explains what ATP binding itself does to SERCA and how nonproductive phosphorylation is prevented in E2.
关键词：ion pump ; SERCA ; ATP binding ; phosphoryl transfer
