1ai1
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(New page: 200px<br /> <applet load="1ai1" size="450" color="white" frame="true" align="right" spinBox="true" caption="1ai1, resolution 2.8Å" /> '''HIV-1 V3 LOOP MIMIC'...)
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Revision as of 11:44, 8 November 2007
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HIV-1 V3 LOOP MIMIC
Overview
Antigenic variation among different HIV-1 isolates has been a major, problem in the development of an effective vaccine against AIDS. Peptide, vaccines incorporating structural elements common to groups of viral, isolates, such as the clade subtypes of HIV-1, hold promise; however, the, design of such immunogens has been hampered by the lack of specific, structural information on the viral proteins to be targeted. As part of a, structure-based approach to this problem, we report the design and, characterization of a conformationally restricted peptide analog (Aib142), of a highly conserved HIV-1 clade-B sequence from the third variable loop, of the membrane glycoprotein gp120. The design strategy incorporates, peptide conformational data derived from crystal structure analysis of an, MN-isolate peptide (RP142) in complex with the Fab fragment (Fab59.1) of a, broadly neutralizing antibody. The synthetic peptide (Aib142) replaces an, alanine residue within the V3 loop epitope sequence GPGRAF by the, conformationally restricted helicogenic alpha-aminoisobutyryl residue. As, expected, the crystal structure of the Fab 59.1-Aib142 complex at 2.8 A, resolution shows that the peptide interacts very similarly with the, neutralizing antibody. Proton nuclear magnetic resonance (NMR) studies, indicate that the free Aib142 peptide is indeed more ordered in solution, with a conformational preference that corresponds to the X-ray structure, of its Fab-bound form. Aib142 thus represents the first step in the design, of conformationally constrained peptide analogs built to mimic, biologically relevant structural forms of HIV-1 neutralization sites.
About this Structure
1AI1 is a Protein complex structure of sequences from Mus musculus. Full crystallographic information is available from OCA.
Reference
Structure-based design of a constrained peptide mimic of the HIV-1 V3 loop neutralization site., Ghiara JB, Ferguson DC, Satterthwait AC, Dyson HJ, Wilson IA, J Mol Biol. 1997 Feb 14;266(1):31-9. PMID:9054968
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