A Darier disease mutation relieves kinetic constraints imposed by the tail of sarco(endo)plasmic reticulum Ca²⁺-ATPase 2b.

ABSTRACT: The sarco(endo)plasmic reticulum Ca²⁺-ATPase (SERCA) 2b isoform possesses an extended C terminus (SERCA2b tail) forming an 11th transmembrane (TM) helix, which slows conformational changes of the Ca²⁺-pump reaction cycle. Here, we report that a Darier disease (DD) mutation of SERCA2b that changes a glutamate to a lysine in the cytoplasmic loop between TM8 and TM9 (E917K) relieves these kinetic constraints. We analyzed the effects of this mutation on the overall reaction and the individual partial reactions of the Ca²⁺ pump compared with the corresponding mutations of the SERCA2a and SERCA1a isoforms, lacking the SERCA2b tail. In addition to a reduced affinity for Ca²⁺, caused by the mutation in all three isoforms examined, we observed a unique en

SUBMITTER: Mikkelsen SA 

PROVIDER: S-EPMC5857973 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature