3n0i

Crystal Structure of Ad37 fiber knob in complex with GD1a oligosaccharide

spinqualitylabelsall models 3n0i, resolution 1.65Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3n0i is a 3 chain structure with sequence from Adenovirus type 37. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: BGC, GAL, NGA, SIA, ZN Gene: L5 (Adenovirus type 37) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Adenovirus type 37 (Ad37) is a leading cause of epidemic keratoconjunctivitis (EKC), a severe and highly contagious ocular disease. Whereas most other adenoviruses infect cells by engaging CD46 or the coxsackie and adenovirus receptor (CAR), Ad37 binds previously unknown sialic acid-containing cell surface molecules. By glycan array screening, we show here that the receptor-recognizing knob domain of the Ad37 fiber protein specifically binds a branched hexasaccharide that is present in the GD1a ganglioside and that features two terminal sialic acids. Soluble GD1a glycan and GD1a-binding antibodies efficiently prevented Ad37 virions from binding and infecting corneal cells. Unexpectedly, the receptor is constituted by one or more glycoproteins containing the GD1a glycan motif rather than the ganglioside itself, as shown by binding, infection and flow cytometry experiments. Molecular modeling, nuclear magnetic resonance and X-ray crystallography reveal that the two terminal sialic acids dock into two of three previously established sialic acid-binding sites in the trimeric Ad37 knob. Surface plasmon resonance analysis shows that the knob-GD1a glycan interaction has high affinity. Our findings therefore form a basis for the design and development of sialic acid-containing antiviral drugs for topical treatment of EKC. The GD1a glycan is a cellular receptor for adenoviruses causing epidemic keratoconjunctivitis.,Nilsson EC, Storm RJ, Bauer J, Johansson SM, Lookene A, Angstrom J, Hedenstrom M, Eriksson TL, Frangsmyr L, Rinaldi S, Willison HJ, Domellof FP, Stehle T, Arnberg N Nat Med. 2010 Dec 12. PMID:21151139 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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