biostudies-literatureSpurrier BNIAID NIH HHSNHLBI NIH HHSNIGMS NIH HHS691-9https://www.ebi.ac.uk/biostudies/studies/S-EPMC3096878biostudies-literatureUnknown19(5)The quaternary neutralizing epitope (QNE) of HIV-1 gp120 is preferentially expressed on the trimeric envelope spikes of intact HIV virions, and QNE-specific monoclonal antibodies (mAbs) potently neutralize HIV-1. Here, we present the crystal structures of the Fabs of human mAb 2909 and macaque mAb 2.5B. Both mAbs have long beta hairpin CDR H3 regions >20 Å in length that are each situated at the center of their respective antigen-binding sites. Computational analysis showed that the paratopes include the whole CDR H3, while additional CDR residues form shallow binding pockets. Structural modeling suggests a way to understand the configuration of QNEs and the antigen-antibody interaction for QNE mAbs. Our data will be useful in designing immunogens that may elicit potent neutralizing QNE AbStructure (London, England : 1993)Structural analysis of human and macaque mAbs 2909 and 2.5B: implications for the configuration of the quaternary neutralizing epitope of HIV-1 gp120.PMC3096878AI036085AI082274GM088118P30 AI027742R01 AI036085R01 AI084119T32 GM088118AI077451HL059725P01 AI082274R01 HL059725AI084119R21 AI077451AI027742Sampson JMLi HKong XPRobinson JO'Neal TGorny MKTotrov MWilliams CZolla-Pazner SSpurrier BfalseStructural analysis of human and macaque mAbs 2909 and 2.5B: implications for the configuration of the quaternary neutralizing epitope of HIV-1 gp120.The quaternary neutralizing epitope (QNE) of HIV-1 gp120 is preferentially expressed on the trimeric envelope spikes of intact HIV virions, and QNE-specific monoclonal antibodies (mAbs) potently neutralize HIV-1. Here, we present the crystal structures of the Fabs of human mAb 2909 and macaque mAb 2.5B. Both mAbs have long beta hairpin CDR H3 regions >20 Å in length that are each situated at the center of their respective antigen-binding sites. Computational analysis showed that the paratopes include the whole CDR H3, while additional CDR residues form shallow binding pockets. Structural modeling suggests a way to understand the configuration of QNEs and the antigen-antibody interaction for QNE mAbs. Our data will be useful in designing immunogens that may elicit potent neutralizing QNE Ab2011-01-01T00:00:00Z2011 May2026-04-15T23:26:00.032Z2026-04-07T14:04:50.759ZS-EPMC30968782156570310.1016/j.str.2011.02.012