1AI1

HIV-1 V3 LOOP MIMIC

Summary for 1AI1

• Entry DOI: 10.2210/pdb1ai1/pdb
• Descriptor: IGG1-KAPPA 59.1 FAB (LIGHT CHAIN), IGG1-KAPPA 59.1 FAB (HEAVY CHAIN), AIB142 (3 entities in total)
• Functional Keywords: complex (antibody-peptide), antibody, constrained hiv-1 v3 loop peptide, immunoglobulin, complex (antibody-peptide) complex, complex (antibody/peptide)
• Biological source: Mus musculus (house mouse); More
• Cellular location: Isoform Secreted: Secreted: P01868; Transmembrane protein gp41: Virion membrane; Single-pass type I membrane protein. Surface protein gp120: Virion membrane; Peripheral membrane protein: P05877
• Total number of polymer chains: 3
• Total formula weight: 50711.86

Authors

Ghiara, J.B.,Wilson, I.A. (deposition date: 1996-11-06, release date: 1997-05-15, Last modification date: 2023-08-02)

Primary citation

Ghiara, J.B.,Ferguson, D.C.,Satterthwait, A.C.,Dyson, H.J.,Wilson, I.A.
Structure-based design of a constrained peptide mimic of the HIV-1 V3 loop neutralization site.
J.Mol.Biol., 266:31-39, 1997

PubMed Abstract: 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.

PubMed: 9054968
DOI: 10.1006/jmbi.1996.0768

Experimental method

X-RAY DIFFRACTION (2.8 Å)