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M9620573.TXT
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1996-02-26
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Document 0573
DOCN M9620573
TI A helical epitope in the C4 domain of HIV glycoprotein 120.
DT 9602
AU Robey FA; Kelson-Harris T; Roller PP; Robert-Guroff M; Peptide and
Immunochemistry Unit, NIDR, National Institutes of; Health, Bethesda,
Maryland 20892, USA.
SO J Biol Chem. 1995 Oct 13;270(41):23918-21. Unique Identifier : AIDSLINE
MED/96025763
AB The fourth conserved domain of the human immunodeficiency virus type 1
(HIV-1) envelope, the C4 region of glycoprotein 120 (gp120), is an
amphipathic stretch of amino acids that, based on mutational analyses,
constitutes a major component of the CD4 binding region in gp120. In the
absence of crystallographic and NMR data on C4 in intact gp120, we
sought to gain insight into C4's conformation and accessibility in gp120
by taking an immunochemical approach. In this study, a peptomer composed
of a repeat peptide of C4 amino acids 419-436 from gp120 of HIV-1MN was
synthesized for use as a conformationally constrained immunogen.
Circular dichroism studies disclosed that the polymerized peptide,
peptomer-(419-436), in 0.01 M Na2HPO4 buffer, pH 7.4, at 25 degrees C
contained a dominant alpha-helical structure (53 +/- 1%) compared with 2
+/- 4% alpha-helical content for the monomeric peptide-(419-436). The
peptomer in Ribi's adjuvant induced the production of rabbit antibodies
that recognized recombinant and native gp120 but, consistent with the
literature, the C4 peptide having no conformational constraints did not.
The experimental results show that only those antibodies formed against
a helical immunogen from C4 will recognize recombinant and native gp120,
and, therefore, the results support the notion that C4 is an alpha-helix
in gp120.
DE Amino Acid Sequence Animal Antibodies Binding Sites, Antibody
Circular Dichroism DNA Mutational Analysis Epitopes/*CHEMISTRY Human
HIV Envelope Protein gp120/*CHEMISTRY/*IMMUNOLOGY HIV-1/*METABOLISM
Molecular Sequence Data Molecular Weight Peptide
Fragments/CHEMISTRY/CHEMICAL SYNTHESIS/IMMUNOLOGY *Protein Structure,
Secondary Rabbits/IMMUNOLOGY Recombinant Proteins/CHEMISTRY/IMMUNOLOGY
Support, U.S. Gov't, P.H.S. JOURNAL ARTICLE
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).