Thirman Jonathan, Rui Huan, Roux Benoît
Department of Chemistry, Gordon Center for Integrative Science, University of Chicago, Chicago, Illinois 60637, United States.
J Phys Chem B. 2021 Mar 25;125(11):2921-2928. doi: 10.1021/acs.jpcb.1c00558. Epub 2021 Mar 15.
A key event in the ATP-driven transport cycle of the calcium pump sarco/endoplasmic reticulum Ca-ATPase (SERCA) occurs when autophosphorylation of the pump with two bound ions Ca triggers a large conformational change that opens a gate on the luminal side of the membrane allowing the release of the ions. It is believed that this conformational transition proceeds through a two-step mechanism, with an initial rearrangement of the three cytoplasmic domains of the pump responsible for ATP binding and hydrolysis followed by the opening of the gate toward the luminal side in the transmembrane region. Here, molecular dynamics computation of the free energy landscapes associated with this transition show how, in response to phosphorylation, the cytoplasmic domains are partially reconfigured into an intermediate state on the path toward the E2 state with a closed luminal gate. It is suggested that the free energy associated with this conformational reorganization must subsequently be used to drive the opening of the gate on the luminal side.
钙泵肌浆网/内质网Ca-ATP酶（SERCA）由ATP驱动的转运循环中的一个关键事件发生在泵与两个结合的钙离子发生自磷酸化时，这会触发一个大的构象变化，从而打开膜腔侧的一个门，使离子得以释放。据信，这种构象转变通过两步机制进行，首先是负责ATP结合和水解的泵的三个胞质结构域发生初始重排，随后跨膜区域向腔侧的门打开。在这里，与这种转变相关的自由能景观的分子动力学计算表明，响应磷酸化，胞质结构域如何在通向具有封闭腔门的E2状态的路径上部分重新配置为中间状态。有人提出，与这种构象重组相关的自由能随后必须用于驱动腔侧门的打开。
