Structural Analysis of Human and Macaque Monoclonal Antibodies 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...
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| Veröffentlicht in: | Structure (London) 2011-12, Vol.19 (5), p.691-699 |
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| container_title | Structure (London) |
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| creator | Spurrier, Brett Sampson, Jared M. Totrov, Maxim Li, Huiguang O'Neal, Timothy Williams, Constance Robinson, James Gorny, Miroslaw K. Zolla-Pazner, Susan Kong, Xiang-Peng |
| description | 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 {angstrom} 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 Abs. |
| doi_str_mv | 10.1016/j.str.2011.02.012 |
| format | Article |
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| source | Cell Press Free Archives; ScienceDirect Journals (5 years ago - present); EZB-FREE-00999 freely available EZB journals; Free Full-Text Journals in Chemistry |
| subjects | 60 APPLIED LIFE SCIENCES AIDS VIRUS BASIC BIOLOGICAL SCIENCES CONFIGURATION CRYSTAL STRUCTURE MONOCLONAL ANTIBODIES RESIDUES SIMULATION |
| title | Structural Analysis of Human and Macaque Monoclonal Antibodies 2909 and 2.5B: Implications for the Configuration of the Quaternary Neutralizing Epitope of HIV-1 gp120 |
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