6PE5

Yeast Vo motor in complex with 2 VopQ molecules

Summary for 6PE5

• Entry DOI: 10.2210/pdb6pe5/pdb
• EMDB information: 20323
• Descriptor: V-type proton ATPase subunit a, vacuolar isoform, V0 assembly protein 1, V-type proton ATPase subunit d, ... (9 entities in total)
• Functional Keywords: complex, transport protein
• Biological source: Vibrio parahaemolyticus; More
• Total number of polymer chains: 17
• Total formula weight: 483766.74

Authors

Peng, W.,Li, Y.,Tomchick, D.R.,Orth, K. (deposition date: 2019-06-20, release date: 2020-05-20, Last modification date: 2024-03-20)

Primary citation

Peng, W.,Casey, A.K.,Fernandez, J.,Carpinone, E.M.,Servage, K.A.,Chen, Z.,Li, Y.,Tomchick, D.R.,Starai, V.J.,Orth, K.
A distinct inhibitory mechanism of the V-ATPase by Vibrio VopQ revealed by cryo-EM.
Nat.Struct.Mol.Biol., 27:589-597, 2020

PubMed Abstract: The Vibrio parahaemolyticus T3SS effector VopQ targets host-cell V-ATPase, resulting in blockage of autophagic flux and neutralization of acidic compartments. Here, we report the cryo-EM structure of VopQ bound to the V subcomplex of the V-ATPase. VopQ inserts into membranes and forms an unconventional pore while binding directly to subunit c of the V-ATPase membrane-embedded subcomplex V. We show that VopQ arrests yeast growth in vivo by targeting the immature V subcomplex in the endoplasmic reticulum (ER), thus providing insight into the observation that VopQ kills cells in the absence of a functional V-ATPase. VopQ is a bacterial effector that has been discovered to inhibit a host-membrane megadalton complex by coincidentally binding its target, inserting into a membrane and disrupting membrane potential. Collectively, our results reveal a mechanism by which bacterial effectors modulate host cell biology and provide an invaluable tool for future studies on V-ATPase-mediated membrane fusion and autophagy.

PubMed: 32424347
DOI: 10.1038/s41594-020-0429-1

Experimental method

ELECTRON MICROSCOPY (3.2 Å)