9BRR
Intact V-ATPase State 3 in synaptophysin knock-out isolated synaptic vesicles
This is a non-PDB format compatible entry.
Summary for 9BRR
| Entry DOI | 10.2210/pdb9brr/pdb |
| EMDB information | 44841 |
| Descriptor | V-type proton ATPase 21 kDa proteolipid subunit c'', V-type proton ATPase subunit H, V-type proton ATPase subunit d 1, ... (16 entities in total) |
| Functional Keywords | v-atpase, synaptic vesicle, membrane protein |
| Biological source | Mus musculus (house mouse) More |
| Total number of polymer chains | 32 |
| Total formula weight | 1047456.31 |
| Authors | |
| 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 Cited by 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: 38838737DOI: 10.1038/s41586-024-07610-x PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (4.5 Å) |
Structure validation
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