Protein-protein interactions within the ensemble, eukaryotic V-ATPase, and its concerted interactions with cellular machineries

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• 作者：Asha Manikkoth Balakrishna¹ ; Malathy Sony Subramanian Manimekalai¹ ; Gerhard Grü ; ber ; ^{ggrueber@ntu.edu.sg" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Bioenergetics ; V-ATPase ; Vacuolar ATPase ; Saccharomyces cerevisiae ; Molecular engine ; Coupling ; Structural biology
• 刊名：Progress in Biophysics and Molecular Biology
• 出版年：2015
• 出版时间：October 2015
• 年：2015
• 卷：119
• 期：1
• 页码：84-93
• 全文大小：2976 K

文摘

The V₁V_O-ATPase (V-ATPase) is the important proton-pump in eukaryotic cells, responsible for pH-homeostasis, pH-sensing and amino acid sensing, and therefore essential for cell growths and metabolism. ATP-cleavage in the catalytic A₃B₃-hexamer of V₁ has to be communicated via several so-called central and peripheral stalk units to the proton-pumping V_O-part, which is membrane-embedded.

A unique feature of V₁V_O-ATPase regulation is its reversible disassembly of the V₁ and V_O domain. Actin provides a network to hold the V₁ in proximity to the V_O, enabling effective V₁V_O-assembly to occur. Besides binding to actin, the 14-subunit V-ATPase interacts with multi-subunit machineries to form cellular sensors, which regulate the pH in cellular compartments or amino acid signaling in lysosomes.

Here we describe a variety of subunit–subunit interactions within the V-ATPase enzyme during catalysis and its protein–protein assembling with key cellular machineries, essential for cellular function.