NMR Mapping of the Antigenic Determinant Recognized by an Anti-Gp120, Human Immunodeficiency Virus Neutralizing Antibody

Zvi, Anat; Kustanovich, I. M.; Feigelson, Daniel; Levy, Rina; Eisenstein, Miri; Matsushita, Shuzo; Richalet-Sécordel, Pascale M.; Regenmortel, M.H.V. Van; Anglister, Jacob

doi:10.1111/j.1432-1033.1995.0178l.x

Cited by 22 publications

(42 citation statements)

References 41 publications

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“…Until the early 90's, predictions of the conformation of V3 loop were based on a neural network approach which yielded for the 35-residue peptide, a -strand -reverse -turn --strand --helix structure [62]. Experimental evidence in solid state through X ray crystallography [49,63,64,[71][72][73][74][75][76][77][78][79][80][81][82][83][84][85] and in solution using NMR spectroscopy [42,67,[86][87][88][89][90][91][92][93][94][95][96][97][98][99][100][101][102][103] suggest that predictable conformational features are present in V3-derived peptide epitopes from various HIV-1 strains.…”

Section: V3 Conformational Featuresmentioning

confidence: 99%

Conformational Properties of HIV-1 gp120/V3 Immunogenic Domains

Galanakis

Spyroulias²,

Rizos³

et al. 2005

CMC

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Infection of target host cells by the human immunodeficiency virus-1 (HIV-1) is a multi-step process involving a series of conformational changes in the viral gp120 and gp41 proteins. Gp120 binding to the main cell receptor, CD4, on the surface of cells expressing this molecule, and interaction with the cell chemokine receptors CCR5 and CXCR4, are among the key events for HIV-1 infection. These steps are crucial for the virus and offer potential therapeutic targets. For this reason, understanding the structure and the physicochemical characteristics of the gp120 in relation to these interactions has drawn much attention. This review article focuses on the biologically important V3 region of the gp120 and summarizes the functional role, the sequence variation and the conformational features of V3 peptides, which are important for co-receptor selectivity, specificity and interaction. Synthetic V3 peptides have been extensively studied by NMR spectroscopy and X-ray crystallography, in solution or in solid state, in their free or bound form, and valuable information was generated with the aim to be exploited in the design of new, effective inhibitors of HIV-1 infection. The features of the potential gp120 interacting sites on the two chemokine co-receptors, CCR5 and CXCR4, are also discussed, and co-receptor blocking molecules under clinical trial are also reported.

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Section: V3 Conformational Featuresmentioning

confidence: 99%

Conformational Properties of HIV-1 gp120/V3 Immunogenic Domains

Galanakis

Spyroulias²,

Rizos³

et al. 2005

CMC

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“…It has been found that the slow dissociation rate of HIV-neutralizing antibody complexes with gp120 is correlated to the efficiency of the virus neutralization (13). Previous 1 H NMR studies of the 0.5β Fab/PND peptide complexes indicated that Lys 5 and Ile 20 constitute the boundaries of the determinant recognized by the antibody, and competitive ELISA measurements using serial deletions of residues from the PND sequence strongly supported the NMR observations (11).…”

Section: Introductionmentioning

confidence: 75%

“…Measurements of the binding constant of 0.5β to gp120 and to the PND peptide revealed similar affinities of 2 × 10 8 and 7 × 10 7 M -1 , respectively (11,12). The dissociation rate of the 0.5β/PND peptide complex is 2 × 10 -3 s -1 at 37°C (11). It has been found that the slow dissociation rate of HIV-neutralizing antibody complexes with gp120 is correlated to the efficiency of the virus neutralization (13).…”

Section: Introductionmentioning

confidence: 75%

“…A chimerical monoclonal antibody that contains the intact variable regions of 0.5β and human constant regions was shown to protect chimpanzees from HIV-1 infection after passive immunization (10). Measurements of the binding constant of 0.5β to gp120 and to the PND peptide revealed similar affinities of 2 × 10 8 and 7 × 10 7 M -1 , respectively (11,12). The dissociation rate of the 0.5β/PND peptide complex is 2 × 10 -3 s -1 at 37°C (11).…”

Section: Introductionmentioning

confidence: 90%

“…The PND peptide truncated by three N-terminal and three C-terminal residues and denoted P1053 herein, binds 0.5β with the same affinity as the whole PND peptide (11). While retaining the full antibody binding properties, the Fv fragment has twice lower molecular weight compared to the Fab, and is therefore by far more suitable for detailed NMR studies.…”

Section: Introductionmentioning

confidence: 99%

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Solution Structure of an Antibody-Bound HIV-1^IIIBV3 Peptide: A Cis Proline Turn Linking Two β-hairpin Strands

Tugarinov

Anglister

2000

Journal of Biomolecular Structure and Dynamics

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The refined solution structure of a peptide representing the full epitope of the HIV-1(IIIB) V3 loop in complex with the anti-gp120 antibody Fv fragment was determined using isotope-filtered and isotope-edited NMR. Both the (15)N-labeled peptide in complex with the unlabeled Fv and the unlabeled peptide complexed with the uniformly (15)N,(13)C-labeled Fv were investigated. The backbone of the bound peptide adopts a well defined β-hairpin conformation with two twisted anti-parallel β-strands linked by a type VI tight turn comprising residues RGPG. The central glycine and proline residues of the turn are linked by a cis peptide bond. (15)N{(1)H} NOE measurements demonstrated that the backbone of the bound peptide including the central QRGPGR loop is well ordered in the bound state. The V3 loop peptide solution structure is significantly different from the peptide conformation in the X-ray structures of three anti-peptide antibody/V3(MN) peptide complexes. These differences seem to be dictated by the antibody dependence and HIV strain-specificity of the V3 peptide fold.

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Structural requirements for and consequences of an antiviral porphyrin binding to the V3 loop of the human immunodeficiency virus (HIV‐1) envelope glycoprotein gp120

Neurath

Strick

Debnath

1995

J of Molecular Recognition

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Several porphyrin derivatives were reported to have anti-HIV-1 activity. Among them, meso-teta(4-carboxyphenyl)porphine (MTCPP) and other carboxyphenyl derivatives were the most potent inhibitors (EC50 <0.7 mu M). MTCPP bound to the HIV-1 envelope glycoprotein gp120 and to full-length V3 loop peptides corresponding to several HIV-1 isolates but not to other peptides from gp120 + gp41. However, it remained possible that MTCPP bound to regions on gp120 which cannot be mimicked by peptides. Further characterization of the binding domain for MTCPP is important for understanding the antiviral activity of porphyrins and for the design of anti-HIV-1 drugs interfering with functions of the virus envelope. Results presented here show that: (i) deletion of the V3 loop from the gp120 sequence resulted in drastically diminished MTCPP binding, suggesting that the V3 loop is the dominant if not the only target site on gp120; (ii) this site was only partially mimicked by full-length V3 loop peptides; (iii) MTCPP binding to the gp120 V3 loop elicited allosteric effects resulting in decreased accessibility of the CD4 receptor binding site; (iv) the binding site for MTCPP lies within the central portion of the V3 loop (KSIHIGPGRAFY for the HIV-1 subtype B consensus sequence) and does not involve directly the GPG apex of the loop. These results may help in designing antiviral compounds with improved activity.

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NMR Mapping of the Antigenic Determinant Recognized by an Anti-Gp120, Human Immunodeficiency Virus Neutralizing Antibody

Cited by 22 publications

References 41 publications

Conformational Properties of HIV-1 gp120/V3 Immunogenic Domains

Conformational Properties of HIV-1 gp120/V3 Immunogenic Domains

Solution Structure of an Antibody-Bound HIV-1^IIIBV3 Peptide: A Cis Proline Turn Linking Two β-hairpin Strands

Structural requirements for and consequences of an antiviral porphyrin binding to the V3 loop of the human immunodeficiency virus (HIV‐1) envelope glycoprotein gp120

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NMR Mapping of the Antigenic Determinant Recognized by an Anti-Gp120, Human Immunodeficiency Virus Neutralizing Antibody

Cited by 22 publications

References 41 publications

Conformational Properties of HIV-1 gp120/V3 Immunogenic Domains

Conformational Properties of HIV-1 gp120/V3 Immunogenic Domains

Solution Structure of an Antibody-Bound HIV-1IIIBV3 Peptide: A Cis Proline Turn Linking Two β-hairpin Strands

Structural requirements for and consequences of an antiviral porphyrin binding to the V3 loop of the human immunodeficiency virus (HIV‐1) envelope glycoprotein gp120

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Product

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Solution Structure of an Antibody-Bound HIV-1^IIIBV3 Peptide: A Cis Proline Turn Linking Two β-hairpin Strands