5dd0

Crystal structures in an anti-HIV antibody lineage from immunization of Rhesus macaques

spinqualitylabelsall models 5dd0, resolution 2.49Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5dd0 is a 3 chain structure with sequence from 9hiv1 and Macmu. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. NonStd Res: ACE, NH2 Related: 5dd1, 5dd3, 5dd5, 5dd6 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Development of an HIV vaccine is a global priority. A major roadblock to a vaccine is an inability to induce protective broadly neutralizing antibodies (bnAbs). HIV gp41 bnAbs have characteristics that predispose them to be controlled by tolerance. We used gp41 2F5 bnAb germline knock-in mice and macaques vaccinated with immunogens reactive with germline precursors to activate neutralizing antibodies. In germline knock-in mice, bnAb precursors were deleted, with remaining anergic B cells capable of being activated by germline-binding immunogens to make gp41-reactive immunoglobulin M (IgM). Immunized macaques made B cell clonal lineages targeted to the 2F5 bnAb epitope, but 2F5-like antibodies were either deleted or did not attain sufficient affinity for gp41-lipid complexes to achieve the neutralization potency of 2F5. Structural analysis of members of a vaccine-induced antibody lineage revealed that heavy chain complementarity-determining region 3 (HCDR3) hydrophobicity was important for neutralization. Thus, gp41 bnAbs are controlled by immune tolerance, requiring vaccination strategies to transiently circumvent tolerance controls. Initiation of immune tolerance-controlled HIV gp41 neutralizing B cell lineages.,Zhang R, Verkoczy L, Wiehe K, Munir Alam S, Nicely NI, Santra S, Bradley T, Pemble CW 4th, Zhang J, Gao F, Montefiori DC, Bouton-Verville H, Kelsoe G, Larimore K, Greenberg PD, Parks R, Foulger A, Peel JN, Luo K, Lu X, Trama AM, Vandergrift N, Tomaras GD, Kepler TB, Moody MA, Liao HX, Haynes BF Sci Transl Med. 2016 Apr 27;8(336):336ra62. doi: 10.1126/scitranslmed.aaf0618. PMID:27122615 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Antibody 3D structures

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