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-Structure paper
Title | The molecular mechanism of sialic acid transport mediated by Sialin. |
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Journal, issue, pages | Sci Adv, Vol. 9, Issue 3, Page eade8346, Year 2023 |
Publish date | Jan 20, 2023 |
Authors | Wenxin Hu / Congwu Chi / Kunhua Song / Hongjin Zheng / |
PubMed Abstract | Malfunction of the sialic acid transporter caused by various genetic mutations in the gene encoding Sialin leads to a spectrum of neurodegenerative conditions called free sialic acid storage ...Malfunction of the sialic acid transporter caused by various genetic mutations in the gene encoding Sialin leads to a spectrum of neurodegenerative conditions called free sialic acid storage disorders. Unfortunately, how Sialin transports sialic acid/proton (H) and how pathogenic mutations impair its function are poorly defined. Here, we present the structure of human Sialin in an inward-facing partially open conformation determined by cryo-electron microscopy, representing the first high-resolution structure of any human SLC17 member. Our analysis reveals two unique features in Sialin: (i) The H coupling/sensing requires two highly conserved Glu residues (E171 and E175) instead of one (E175) as implied in previous studies; and (ii) the normal function of Sialin requires the stabilization of a cytosolic helix, which has not been noticed in the literature. By mapping known pathogenic mutations, we provide mechanistic explanations for corresponding functional defects. We propose a structure-based mechanism for sialic acid transport mediated by Sialin. |
External links | Sci Adv / PubMed:36662855 / PubMed Central |
Methods | EM (single particle) |
Resolution | 3.4 Å |
Structure data | EMDB-27755, PDB-8dwi: |
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Keywords | MEMBRANE PROTEIN / sialic acid transport / solute carrier transporter |