7qe5

Structure of the membrane domains of the sialic acid TRAP transporter HiSiaQM from Haemophilus influenzae

spinqualitylabelsall models 7qe5, resolution 4.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7qe5 is a 2 chain structure with sequence from Haemophilus influenzae and Vicugna pacos. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 4.7Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function SIAT1_HAEIN Part of the tripartite ATP-independent periplasmic (TRAP) transport system SiaPT involved in the uptake of sialic acid (N-acetyl-beta-neuraminate). N-Acetylneuraminate can then be incorporated into the lipopolysaccharides as a terminal non-reducing sugar, protecting the bacterium from complement-mediated killing by normal human serum. Publication Abstract from PubMed Tripartite ATP-independent periplasmic (TRAP) transporters are found widely in bacteria and archaea and consist of three structural domains, a soluble substrate-binding protein (P-domain), and two transmembrane domains (Q- and M-domains). HiSiaPQM and its homologs are TRAP transporters for sialic acid and are essential for host colonization by pathogenic bacteria. Here, we reconstitute HiSiaQM into lipid nanodiscs and use cryo-EM to reveal the structure of a TRAP transporter. It is composed of 16 transmembrane helices that are unexpectedly structurally related to multimeric elevator-type transporters. The idiosyncratic Q-domain of TRAP transporters enables the formation of a monomeric elevator architecture. A model of the tripartite PQM complex is experimentally validated and reveals the coupling of the substrate-binding protein to the transporter domains. We use single-molecule total internal reflection fluorescence (TIRF) microscopy in solid-supported lipid bilayers and surface plasmon resonance to study the formation of the tripartite complex and to investigate the impact of interface mutants. Furthermore, we characterize high-affinity single variable domains on heavy chain (VHH) antibodies that bind to the periplasmic side of HiSiaQM and inhibit sialic acid uptake, providing insight into how TRAP transporter function might be inhibited in vivo. Structural and mechanistic analysis of a tripartite ATP-independent periplasmic TRAP transporter.,Peter MF, Ruland JA, Depping P, Schneberger N, Severi E, Moecking J, Gatterdam K, Tindall S, Durand A, Heinz V, Siebrasse JP, Koenig PA, Geyer M, Ziegler C, Kubitscheck U, Thomas GH, Hagelueken G Nat Commun. 2022 Aug 4;13(1):4471. doi: 10.1038/s41467-022-31907-y. PMID:35927235 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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