Prediction of the secondary structure of HIV-1 gp120

Hansen, Jan Erik; Lund, Ole; Nielsen, Jens; Brunak, Søren

doi:10.1002/(sici)1097-0134(199605)25:1<1::aid-prot1>3.0.co;2-n

Cited by 34 publications

(26 citation statements)

References 73 publications

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“…This implies that the fusion of proteins expressing two components binding to different sites on gp120 per se does not guarantee enhanced bioactivity. The amino acids involved in CD4 recognition distribute discontinuously around C2, C3 and V5 regions of gp120 (4,24,45), whereas DC-SIGN interacts with discontinuously distributed high-mannose oligosaccharides on gp120 (20). Short linkers likely hindered the two moieties of the fusion proteins from simultaneously interacting with gp120, while a linker with suitable length could render CLDs with higher gp120-binding avidity and better anti-HIV potency.…”

Section: Discussionmentioning

confidence: 99%

Bifunctional CD4–DC-SIGN Fusion Proteins Demonstrate Enhanced Avidity to gp120 and Inhibit HIV-1 Infection and Dissemination

Yang

et al. 2012

Antimicrob Agents Chemother

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Section: Discussionmentioning

confidence: 99%

Bifunctional CD4–DC-SIGN Fusion Proteins Demonstrate Enhanced Avidity to gp120 and Inhibit HIV-1 Infection and Dissemination

Yang

et al. 2012

Antimicrob Agents Chemother

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“…The function of such a structural element, if one exists, is presently unknown, however. The precise predicted secondary structure adopted by the GPGR residues is a type II ␤-turn (6,7).…”

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confidence: 99%

The Binding of a Glycoprotein 120 V3 Loop Peptide to HIV-1 Neutralizing Antibodies

Wu¹,

MacKenzie²,

Durda³

et al. 2000

Journal of Biological Chemistry

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The structural and antigenic properties of a peptide ("CRK") derived from the V3 loop of HIV-1 gp120 protein were studied using NMR and SPR techniques. The sequence of CRK corresponds to the central portion of the V3 loop containing the highly conserved "GPGR" residue sequence. Although the biological significance of this conserved sequence is unknown, the adoption of conserved secondary structure (type II ␤-turn) in this region has been proposed. The tendency of CRK (while free or conjugated to protein), to adopt such structure and the influence of such structure upon CRK antigenicity were investigated by NMR and SPR, respectively. Regardless of conjugation, CRK is conformationally averaged in solution but a weak tendency of the CRK "GPGR" residues to adopt a ␤-turn conformation was observed after conjugation. The influence of GPGR structure upon CRK antigenicity was investigated by measuring the affinities of two cognate antibodies: "5023A" and "5025A," for CRK, protein-conjugated CRK and gp120 protein. Each antibody bound to all the antigens with nearly the same affinity. From these data, it appears that: (a) antibody binding most likely involves an induced fit of the peptide and (b) the gp120 V3 loop is probably conformationally heterogeneous. Since 5023A and 5025A are HIV-1 neutralizing antibodies, neutralization in these cases appears to be independent of adopted GPGR ␤-turn structure. The principal neutralizing determinant (PND)1 of HIV-1 has been mapped to the third hypervariable (V3) loop of the HIV-1 envelope protein, gp120 (1). PND-derived peptides are used as immunogens to elicit antibodies that possess HIV-1 virus neutralization capabilities (2, 3). The binding of neutralizing antibodies blocks virus entry into the host cell but does not prevent binding of HIV-1 to its primary cell receptor protein, CD4 (4, 5). Although the V3 loop represents an important target for the development of vaccines against AIDS, its high sequence variability also makes it a very problematic one (6). Nonetheless, the occurrence of the highly conserved residue sequence, "GPGR," at the tip of the V3 loop has raised the possibility that these residues make up a conserved secondary structural element in gp120. The function of such a structural element, if one exists, is presently unknown, however. The precise predicted secondary structure adopted by the GPGR residues is a type II ␤-turn (6, 7).In order to determine whether the conserved GPGR sequence confers certain secondary structural tendencies upon this region of the V3 loop, numerous NMR studies were conducted upon a variety of V3 loop-derived peptides (8 -21). These peptides were shown to have only low density populations of folded structure and to be conformationally averaged in solution. Despite the report of a "core" gp120 protein complex crystal structure, this complex was prepared using a form of gp120 which lacked most of the hypervariable loops including V3 (22). Information regarding the actual three-dimensional structure of the V3 loop in native gp120 is theref...

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“…Consequently, the trifluoroethanol/aqueous mixture may very well mimic the hydrophobic environment of the gp120 C5 domain in vivo. Interestingly, the presence of helix at residues 500-511 was predicted for HIV gp120 by various methods of secondary structure prediction [30] and thus the C5 propensity for helical structure is not surprising. Importantly, we have shown by fluorescence titration that HIV C5 directly interacts with the HIV gp41 ectodomain in the presence of cosolvent, suggesting that the C5 structure presented herein is physiologically relevant.…”

Section: Discussionmentioning

confidence: 99%

Solution structure of the HIV gp120 C5 Domain

Guilhaudis

Jacobs

Caffrey

2002

European Journal of Biochemistry

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In HIV the viral envelope protein is processed by a host cell protease to form gp120 and gp41. The C1 and C5 domains of gp120 are thought to directly interact with gp41 but are largely missing from the available X-ray structure. Biophysical studies of the HIV gp120 C5 domain (residues 489-511 of HIV-1 strain HXB2), which corresponds to the carboxy terminal region of gp120, have been undertaken. CD studies of the C5 domain suggest that it is unstructured in aqueous solutions but partially helical in trifluoroethanol/ aqueous and hexafluoroisopropanol/aqueous buffers. The solution structure of the C5 peptide in 40% trifluoroethanol/ aqueous buffer was determined by NMR spectroscopy. The resulting structure is a turn helix structural motif, consistent with the CD results. Fluorescence titration experiments suggest that HIV C5 forms a 1 : 1 complex with the HIV gp41 ectodomain in the presence of cosolvent with an apparent K d of 1.0 lM. The absence of complex formation in the absence of cosolvent indicates that formation of the turn-helix structural motif of C5 is necessary for complex formation. Examination of the C5 structure provides insight into the interaction between gp120 and gp41 and provides a possible target site for future drug therapies designed to disrupt the gp120/gp41 complex. In addition, the C5 structure lends insight into the site of HIV envelope protein maturation by the host enzymes furin and PC7, which provides other possible targets for drug therapies.

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Prediction of the secondary structure of HIV-1 gp120

Cited by 34 publications

References 73 publications

Bifunctional CD4–DC-SIGN Fusion Proteins Demonstrate Enhanced Avidity to gp120 and Inhibit HIV-1 Infection and Dissemination

Bifunctional CD4–DC-SIGN Fusion Proteins Demonstrate Enhanced Avidity to gp120 and Inhibit HIV-1 Infection and Dissemination

The Binding of a Glycoprotein 120 V3 Loop Peptide to HIV-1 Neutralizing Antibodies

Solution structure of the HIV gp120 C5 Domain

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