Year: 2020
Type: article
Abstract: -ATPases (V-ATPase) hydrolyze ATP to pump protons across the plasma or intracellular membrane, secreting acids to the lumen or acidifying intracellular compartments. It has been implicated in tumor metastasis, renal tubular acidosis, and osteoporosis. Here, we report two cryo-EM structures of the intact V-ATPase from bovine brain with all the subunits including the subunit H, which is essential for ATPase activity. Two type-I transmembrane proteins, Ac45 and (pro)renin receptor, along with subunit c", constitute the core of the c-ring. Three different conformations of A/B heterodimers suggest a mechanism for ATP hydrolysis that triggers a rotation of subunits DF, inducing spinning of subunit d with respect to the entire c-ring. Moreover, many lipid molecules have been observed in the Vo domain to mediate the interactions between subunit c, c", (pro)renin receptor, and Ac45. These two structures reveal unique features of mammalian V-ATPase and suggest a mechanism of V1-Vo torque transmission.
Source: Nature Communications
Institution: The University of Texas Southwestern Medical Center
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,380
Funders: U.S. Department of Health and Human Services, Welch Foundation, Damon Runyon Cancer Research Foundation, Cancer Prevention and Research Institute of Texas, University of Texas Southwestern Medical Center, National Institutes of Health, National Heart, Lung, and Blood Institute, National Institute of General Medical Sciences
Awards: Establish a New Cryo-Electron Microscopy Core Facility and Service for Structure Determination at UT Southwestern Medical Center, G1641438043, G2103742737, Molecular Basis of Cholesterol Metabolism, G4059366925, G458762562, G5186773050, G6035979156, Role of ABCG1, ABCG5 and ABCG8 in Sterol Metabolism, G7508714112, G9000080722, G9000340545, G9349655
OpenAlex ID: W3047235014