9BRY

V0-only V-ATPase in synaptophysin gene knock-out mouse brain isolated synaptic vesicles

Summary for 9BRY

• Entry DOI: 10.2210/pdb9bry/pdb
• EMDB information: 44845
• Descriptor: V-type proton ATPase subunit S1, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (12 entities in total)
• Functional Keywords: v0only v-atpase, synaptic vesicle, membrane protein
• Biological source: Mus musculus (house mouse); More
• Total number of polymer chains: 16
• Total formula weight: 407287.49

Authors

Wang, C.,Jiang, W.,Yang, K.,Wang, X.,Guo, Q.,Brunger, A.T. (deposition date: 2024-05-12, release date: 2024-06-19, Last modification date: 2024-11-20)

Primary citation

Wang, C.,Jiang, W.,Leitz, J.,Yang, K.,Esquivies, L.,Wang, X.,Shen, X.,Held, R.G.,Adams, D.J.,Basta, T.,Hampton, L.,Jian, R.,Jiang, L.,Stowell, M.H.B.,Baumeister, W.,Guo, Q.,Brunger, A.T.
Structure and topography of the synaptic V-ATPase-synaptophysin complex.
Nature, 631:899-904, 2024

PubMed Abstract: Synaptic vesicles are organelles with a precisely defined protein and lipid composition, yet the molecular mechanisms for the biogenesis of synaptic vesicles are mainly unknown. Here we discovered a well-defined interface between the synaptic vesicle V-ATPase and synaptophysin by in situ cryo-electron tomography and single-particle cryo-electron microscopy of functional synaptic vesicles isolated from mouse brains. The synaptic vesicle V-ATPase is an ATP-dependent proton pump that establishes the proton gradient across the synaptic vesicle, which in turn drives the uptake of neurotransmitters. Synaptophysin and its paralogues synaptoporin and synaptogyrin belong to a family of abundant synaptic vesicle proteins whose function is still unclear. We performed structural and functional studies of synaptophysin-knockout mice, confirming the identity of synaptophysin as an interaction partner with the V-ATPase. Although there is little change in the conformation of the V-ATPase upon interaction with synaptophysin, the presence of synaptophysin in synaptic vesicles profoundly affects the copy number of V-ATPases. This effect on the topography of synaptic vesicles suggests that synaptophysin assists in their biogenesis. In support of this model, we observed that synaptophysin-knockout mice exhibit severe seizure susceptibility, suggesting an imbalance of neurotransmitter release as a physiological consequence of the absence of synaptophysin.

PubMed: 38838737
DOI: 10.1038/s41586-024-07610-x

Experimental method

ELECTRON MICROSCOPY (3.6 Å)