9AYB
Structure of Apo Sialin S61A mutant
Summary for 9AYB
| Entry DOI | 10.2210/pdb9ayb/pdb |
| EMDB information | 43984 |
| Descriptor | Sialin (1 entity in total) |
| Functional Keywords | transporter, membrane protein |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 55665.14 |
| Authors | Schmiege, P.,Li, X. (deposition date: 2024-03-07, release date: 2024-05-29, Last modification date: 2024-12-11) |
| Primary citation | Schmiege, P.,Donnelly, L.,Elghobashi-Meinhardt, N.,Lee, C.H.,Li, X. Structure and inhibition of the human lysosomal transporter Sialin. Nat Commun, 15:4386-4386, 2024 Cited by PubMed Abstract: Sialin, a member of the solute carrier 17 (SLC17) transporter family, is unique in its ability to transport not only sialic acid using a pH-driven mechanism, but also transport mono and diacidic neurotransmitters, such as glutamate and N-acetylaspartylglutamate (NAAG), into synaptic vesicles via a membrane potential-driven mechanism. While most transporters utilize one of these mechanisms, the structural basis of how Sialin transports substrates using both remains unclear. Here, we present the cryogenic electron-microscopy structures of human Sialin: apo cytosol-open, apo lumen-open, NAAG-bound, and inhibitor-bound. Our structures show that a positively charged cytosol-open vestibule accommodates either NAAG or the Sialin inhibitor Fmoc-Leu-OH, while its luminal cavity potentially binds sialic acid. Moreover, functional analyses along with molecular dynamics simulations identify key residues in binding sialic acid and NAAG. Thus, our findings uncover the essential conformational states in NAAG and sialic acid transport, demonstrating a working model of SLC17 transporters. PubMed: 38782953DOI: 10.1038/s41467-024-48535-3 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.19 Å) |
Structure validation
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