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- Title
Tuning Protein Dynamics to Sense Rapid Endoplasmic‐Reticulum Calcium Dynamics.
- Authors
Deng, Xiaonan; Yao, Xin‐Qiu; Berglund, Ken; Dong, Bin; Ouedraogo, Daniel; Ghane, Mohammad A.; Zhuo, You; McBean, Cheyenne; Wei, Zheng Zachory; Gozem, Samer; Yu, Shan P.; Wei, Ling; Fang, Ning; Mabb, Angela M.; Gadda, Giovanni; Hamelberg, Donald; Yang, Jenny J.
- Abstract
Multi‐scale calcium (Ca2+) dynamics, exhibiting wide‐ranging temporal kinetics, constitutes a ubiquitous mode of signal transduction. We report a novel endoplasmic‐reticulum (ER)‐targeted Ca2+ indicator, R‐CatchER, which showed superior kinetics in vitro (koff≥2×103 s−1, kon≥7×106 M−1 s−1) and in multiple cell types. R‐CatchER captured spatiotemporal ER Ca2+ dynamics in neurons and hotspots at dendritic branchpoints, enabled the first report of ER Ca2+ oscillations mediated by calcium sensing receptors (CaSRs), and revealed ER Ca2+‐based functional cooperativity of CaSR. We elucidate the mechanism of R‐CatchER and propose a principle to rationally design genetically encoded Ca2+ indicators with a single Ca2+‐binding site and fast kinetics by tuning rapid fluorescent‐protein dynamics and the electrostatic potential around the chromophore. The design principle is supported by the development of G‐CatchER2, an upgrade of our previous (G‐)CatchER with improved dynamic range. Our work may facilitate protein design, visualizing Ca2+ dynamics, and drug discovery.
- Subjects
PROTEIN engineering; CALCIUM; ELECTRIC potential; CELLULAR signal transduction; CATCHERS (Baseball)
- Publication
Angewandte Chemie, 2021, Vol 133, Issue 43, p23477
- ISSN
0044-8249
- Publication type
Article
- DOI
10.1002/ange.202108443