Order-disorder transitions of cytoplasmic N-termini in the mechanisms of P-type ATPases,Faraday Discussions

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Order-disorder transitions of cytoplasmic N-termini in the mechanisms of P-type ATPases
Faraday Discussions ( IF 3.3 ) Pub Date : 2020-09-01 , DOI: 10.1039/d0fd00040j
Khondker R Hossain ₁ , Daniel Clayton ₁ , Sophia C Goodchild ₂ , Alison Rodger ₂ , Richard J Payne ₁ , Flemming Cornelius ₃ , Ronald J Clarke _{1,

4}

Affiliation

Membrane protein structure and function are modulated via interactions with their lipid environment. This is particularly true for integral membrane pumps, the P-type ATPases. These ATPases play vital roles in cell physiology, where they are associated with the transport of cations and lipids, thereby generating and maintaining crucial (electro-)chemical potential gradients across the membrane. Several pumps (Na⁺, K⁺-ATPase, H⁺, K⁺-ATPase and the plasma membrane Ca²⁺-ATPase) which are located in the asymmetric animal plasma membrane have been found to possess polybasic (lysine-rich) domains on their cytoplasmic surfaces, which are thought to act as phosphatidylserine (PS) binding domains. In contrast, the sarcoplasmic reticulum Ca²⁺-ATPase, located within an intracellular organelle membrane, does not possess such a domain. Here we focus on the lysine-rich N-termini of the plasma-membrane-bound Na⁺, K⁺- and H⁺, K⁺-ATPases. Synthetic peptides corresponding to the N-termini of these proteins were found, via quartz crystal microbalance and circular dichroism measurements, to interact via an electrostatic interaction with PS-containing membranes, thereby undergoing an increase in helical or other secondary structure content. As well as influencing ion pumping activity, it is proposed that this interaction could provide a mechanism for sensing the lipid asymmetry of the plasma membrane, which changes drastically when a cell undergoes apoptosis, i.e. programmed cell death. Thus, polybasic regions of plasma membrane-bound ion pumps could potentially perform the function of a “death sensor”, signalling to a cell to reduce pumping activity and save energy.

中文翻译：

P型ATP酶机制中细胞质N末端的有序-无序转变

膜蛋白的结构和功能通过与其脂质环境的相互作用进行调节。对于集成膜泵 P 型 ATP 酶来说尤其如此。这些 ATP 酶在细胞生理学中起着至关重要的作用，它们与阳离子和脂质的运输有关，从而产生和维持跨膜的关键（电）化学势梯度。几个泵（Na ⁺、K ⁺ -ATPase、H ⁺、K ⁺ -ATPase 和质膜 Ca ²⁺已发现位于不对称动物质膜中的-ATPase）在其细胞质表面上具有多元（富含赖氨酸）结构域，这些结构域被认为充当磷脂酰丝氨酸（PS）结合结构域。相反，位于细胞内细胞器膜内的肌浆网Ca ²⁺ -ATP酶不具有这样的结构域。在这里，我们关注质膜结合的 Na ⁺、K ⁺ - 和 H ⁺、K ⁺ -ATP酶的富含赖氨酸的 N 末端。通过石英晶体微量天平和圆二色性测量，发现与这些蛋白质的 N 末端相对应的合成肽通过以下方式相互作用与含 PS 的膜发生静电相互作用，从而增加螺旋或其他二级结构的含量。除了影响离子泵活性外，还提出这种相互作用可以提供一种机制来感知质膜的脂质不对称性，当细胞经历凋亡即程序性细胞死亡时，这种不对称性会发生巨大变化。因此，质膜结合离子泵的多碱基区域可能会发挥“死亡传感器”的功能，向细胞发出信号以减少泵送活动并节省能量。

更新日期：2020-09-01

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