TY - JOUR
T1 - Cryo-EM structures of intact V-ATPase from bovine brain
AU - Wang, Rong
AU - Long, Tao
AU - Hassan, Abdirahman
AU - Wang, Jin
AU - Sun, Yingyuan
AU - Xie, Xiao Song
AU - Li, Xiaochun
N1 - Funding Information:
This research was done in the memory of our colleague Dennis K. Stone. The data were collected at the UT Southwestern Medical Center Cryo-EM Facility (funded in part by the CPRIT Core Facility Support Award RP170644); we thank D. Stoddard for assistance in data collection. We thank E. Debler for discussion during paper preparation and A. Lemoff at the UT Southwestern Proteomics Core for mass spectrometry identification. This work was supported by NIH grant R01 HL072304 (to X.X.), P01 HL020948, the Endowed Scholars Program in Medical Science of UT Southwestern Medical Center, O’Donnell Junior Faculty Funds, Welch Foundation (I-1957) (to X.L.). X.L. is a Damon Runyon-Rachleff Innovator supported by the Damon Runyon Cancer Research Foundation (DRR-53-19) and Rita C. and William P. Clements Jr. Scholar in Biomedical Research at UT Southwestern Medical Center.
Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12/1
Y1 - 2020/12/1
N2 - The vacuolar-type H+-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.
AB - The vacuolar-type H+-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.
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U2 - 10.1038/s41467-020-17762-9
DO - 10.1038/s41467-020-17762-9
M3 - Article
C2 - 32764564
AN - SCOPUS:85089159400
SN - 2041-1723
VL - 11
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 3921
ER -