8E22
VPS37A_21-148
Summary for 8E22
| Entry DOI | 10.2210/pdb8e22/pdb |
| NMR Information | BMRB: 31039 |
| Descriptor | Vacuolar protein sorting-associated protein 37A (1 entity in total) |
| Functional Keywords | escrt, autophagy, structural protein |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 14571.69 |
| Authors | |
| Primary citation | Ye, Y.,Liang, X.,Wang, G.,Bewley, M.C.,Hamamoto, K.,Liu, X.,Flanagan, J.M.,Wang, H.G.,Takahashi, Y.,Tian, F. Identification of membrane curvature sensing motifs essential for VPS37A phagophore recruitment and autophagosome closure. Commun Biol, 7:334-334, 2024 Cited by PubMed Abstract: VPS37A, an ESCRT-I complex component, is required for recruiting a subset of ESCRT proteins to the phagophore for autophagosome closure. However, the mechanism by which VPS37A is targeted to the phagophore remains obscure. Here, we demonstrate that the VPS37A N-terminal domain exhibits selective interactions with highly curved membranes, mediated by two membrane-interacting motifs within the disordered regions surrounding its Ubiquitin E2 variant-like (UEVL) domain. Site-directed mutations of residues in these motifs disrupt ESCRT-I localization to the phagophore and result in defective phagophore closure and compromised autophagic flux in vivo, highlighting their essential role during autophagy. In conjunction with the UEVL domain, we postulate that these motifs guide a functional assembly of the ESCRT machinery at the highly curved tip of the phagophore for autophagosome closure. These results advance the notion that the distinctive membrane architecture of the cup-shaped phagophore spatially regulates autophagosome biogenesis. PubMed: 38491121DOI: 10.1038/s42003-024-06026-7 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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