Alanine substitution of two arginines in amino terminus of V3 of SIV disrupts CD4 binding whereas a similar replacement of two amino acids, lysine and arginine, in the carboxyl half of V3 prevents binding of a neutralizing monoclonal antibody. NLM AIDSLINE Important note: Information in this article was accurate in 1996. The state of the art may have changed since the publication date.

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Alanine substitution of two arginines in amino terminus of V3 of SIV disrupts CD4 binding whereas a similar replacement of two amino acids, lysine and arginine, in the carboxyl half of V3 prevents binding of a neutralizing monoclonal antibody.

AIDS Res Hum Retroviruses. 1995 Sep;11(9):1101-5. Unique Identifier : AIDSLINE MED/96089217
Javaherian K; Zuchowski L; Clark FT; Repligen Corporation, Cambridge, Massachusetts 02139, USA.

Abstract: A series of amino acid substitutions were carried out in the V3 loop of SIV gp120 to investigate their effects on binding of the envelope to CD4 and neutralizing monoclonal antibodies. Alanine replacement of two adjacent arginines at the amino terminus of V3 resulted in a molecule that bound neither sCD4 nor conformation-dependent neutralizing monoclonal KK5 and KK9. A similar substitution of two amino acids, lysine and arginine, in the carboxyl half of V3 disrupted binding to KK9 without affecting CD4 binding. Removal of V3 from the envelope gave rise to a molecule that was not secreted. These data suggest a close linkage between V3 and CD4 binding domains of gp120, although neutralizing antibodies directed to V3 do not block binding of gp120 to CD4. We propose that differences in the modes of interactions of the V3 disulfide loops with CD4 in SIV and HIV may be responsible for the observed different neutralizing properties of the two V3 loops.
Keywords: Amino Acid Sequence Animal Antibodies, Monoclonal/METABOLISM Antibodies, Viral/METABOLISM Antigens, CD4/*METABOLISM Binding Sites Cell Line HIV Envelope Protein gp120/CHEMISTRY/*GENETICS/*IMMUNOLOGY Models, Molecular Molecular Sequence Data Mutagenesis, Site-Directed Neutralization Tests SIV/*GENETICS/*IMMUNOLOGY JOURNAL ARTICLEKWDaminoacidsequenceanimalantibodies,monoclonal/metabolismantibodies,viral/metabolismantigens,cd4/KWDmetabolismbindingsitescelllinehivenvelopeproteingp120/chemistry/KWDgenetics/KWDimmunologymodels,molecularmolecularsequencedatamutagenesis,site-directedneutralizationtestssiv/KWDgenetics/KWDimmunologyjournalarticle
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M9651089

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