2xra

crystal structure of the HK20 Fab in complex with a gp41 mimetic 5- Helix

spinqualitylabelsall models 2xra, resolution 2.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2xra is a 3 chain structure with sequence from Homo sapiens and Synthetic construct sequences. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Related: 1df4, 1df5, 1dlb, 1opn, 1opw, 1gc1, 1opt, 1k33, 1rzj, 1g9m, 1k34, 1aik, 2cmr, 1gzl, 1mzi Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed The human monoclonal antibody (mAb) HK20 neutralizes a broad spectrum of primary HIV-1 isolates by targeting the highly conserved heptad repeat 1 (HR1) of gp41, which is transiently exposed during HIV-1 entry. Here we present the crystal structure of the HK20 Fab in complex with a gp41 mimetic 5-Helix at 2.3 A resolution. HK20 employs its heavy chain CDR H2 and H3 loops to bind into a conserved hydrophobic HR1 pocket that is occupied by HR2 residues in the gp41 post fusion conformation. Compared to the previously described HR1-specific mAb D5, HK20 approaches its epitope with a different angle which might favor epitope access and thus contribute to its higher neutralization breadth and potency. Comparison of the neutralization activities of HK20 IgG, Fab and scFv employing both single cycle and multiple cycle neutralization assays revealed much higher potencies for the smaller Fab and scFv over IgG, implying that the target site is difficult to access for complete antibodies. Nevertheless, two thirds of sera from HIV-1 infected individuals contain significant titers of HK20-inhibiting antibodies. The breadth of neutralization of primary isolates across all clades, the higher potencies for C-clade viruses and the targeting of a distinct site as compared to the fusion inhibitor T-20 demonstrate the potential of HK20 scFv as a therapeutic tool. Crystal Structure and Size-Dependent Neutralization Properties of HK20, a Human Monoclonal Antibody Binding to the Highly Conserved Heptad Repeat 1 of gp41.,Sabin C, Corti D, Buzon V, Seaman MS, Lutje Hulsik D, Hinz A, Vanzetta F, Agatic G, Silacci C, Mainetti L, Scarlatti G, Sallusto F, Weiss R, Lanzavecchia A, Weissenhorn W PLoS Pathog. 2010 Nov 18;6(11):e1001195. PMID:21124990 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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