8R8Q
Lysosomal peptide transporter
Summary for 8R8Q
| Entry DOI | 10.2210/pdb8r8q/pdb |
| EMDB information | 19006 |
| Descriptor | Major facilitator superfamily domain-containing protein 1, Glycosylated lysosomal membrane protein, 2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total) |
| Functional Keywords | mfs transporter, mfsd family, nutrition transporter, lysosomal transporter, outward open, membrane protein |
| Biological source | Mus musculus (house mouse) More |
| Total number of polymer chains | 2 |
| Total formula weight | 99974.30 |
| Authors | Jungnickel, K.E.J.,Loew, C. (deposition date: 2023-11-29, release date: 2024-05-01, Last modification date: 2024-11-06) |
| Primary citation | Jungnickel, K.E.J.,Guelle, O.,Iguchi, M.,Dong, W.,Kotov, V.,Gabriel, F.,Debacker, C.,Dairou, J.,McCort-Tranchepain, I.,Laqtom, N.N.,Chan, S.H.,Ejima, A.,Sato, K.,Massa Lopez, D.,Saftig, P.,Mehdipour, A.R.,Abu-Remaileh, M.,Gasnier, B.,Low, C.,Damme, M. MFSD1 with its accessory subunit GLMP functions as a general dipeptide uniporter in lysosomes. Nat.Cell Biol., 26:1047-1061, 2024 Cited by PubMed Abstract: The lysosomal degradation of macromolecules produces diverse small metabolites exported by specific transporters for reuse in biosynthetic pathways. Here we deorphanized the major facilitator superfamily domain containing 1 (MFSD1) protein, which forms a tight complex with the glycosylated lysosomal membrane protein (GLMP) in the lysosomal membrane. Untargeted metabolomics analysis of MFSD1-deficient mouse lysosomes revealed an increase in cationic dipeptides. Purified MFSD1 selectively bound diverse dipeptides, while electrophysiological, isotope tracer and fluorescence-based studies in Xenopus oocytes and proteoliposomes showed that MFSD1-GLMP acts as a uniporter for cationic, neutral and anionic dipeptides. Cryoelectron microscopy structure of the dipeptide-bound MFSD1-GLMP complex in outward-open conformation characterized the heterodimer interface and, in combination with molecular dynamics simulations, provided a structural basis for its selectivity towards diverse dipeptides. Together, our data identify MFSD1 as a general lysosomal dipeptide uniporter, providing an alternative route to recycle lysosomal proteolysis products when lysosomal amino acid exporters are overloaded. PubMed: 38839979DOI: 10.1038/s41556-024-01436-5 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (4.08 Å) |
Structure validation
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