Characterization of a discontinuous epitope of the HIV envelope protein gp120 recognized by a human monoclonal antibody using chemical modification and mass spectrometric analysis |
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Authors: | Christine Hager-Braun Elisabeth O Hochleitner Miroslaw K Gorny Susan Zolla-Pazner Rachelle J Bienstock Kenneth B Tomer |
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Institution: | 1.National Institute of Environmental Health Sciences,NIH, DHHS, Laboratory of Structural Biology,Research Triangle Park,USA;2.New York University School of Medicine and Veterans Affairs New York Harbor Healthcare System,New York,USA |
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Abstract: | A subset of the neutralizing anti-HIV antibodies recognize epitopes on the envelope protein gp120 of the human immunodeficiency
virus. These epitopes are exposed during conformational changes when gp120 binds to its primary receptor CD4. Based on chemical
modification of lysine and arginine residues followed by mass spectrometric analysis, we determined the epitope on gp120 recognized
by the human monoclonal antibody 559/64-D, which was previously found to be specific for the CD4 binding domain. Twenty-four
lysine and arginine residues in recombinant full-length glycosylated gp120 were characterized; the relative reactivities of
two lysine residues and five arginine residues were affected by the binding of 559/64-D. The data show that the epitope is
discontinuous and is located in the proximity of the CD4-binding site. Additionally, the reactivities of a residue that is
located in the secondary receptor binding region and several residues distant from the CD4 binding site were also altered
by Ab binding. These data suggest that binding of 559/64-D induced conformational changes which result in altered surface
exposure of specific amino acids distant from the CD4-binding site. Consequently, binding of 559/64-D to gp120 affects not
only the CD4-binding site, which is recognized as the epitope, but appears to have a global effect on surface exposed residues
of the full-length glycosylated gp120. |
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