Crystal structure of a human immunodeficiency virus type 1 neutralizing antibody, 50.1, in complex with its V3 loop peptide antigen.

Rini, James M.; Stanfield, Robyn L.; Stura, E.A.; Salinas, Paul A.; Profy, Albert T.; Wilson, Ian A.

doi:10.1073/pnas.90.13.6325

Cited by 200 publications

(146 citation statements)

References 24 publications

(28 reference statements)

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“…Our data agree with several previous NMR studies [ 33 35,19] and a crystal structure of a V3 peptide in the presence of an antibody [36] which have described structural elements present in various V3 loop peptides, in particular the highly conserved [~-turn around the -GPG(X)-segment. Several NOEs between the sugar and the peptide backbone were observed as outlined in Table 2.…”

Section: Dnn(ii+l) and Weak Dan(ii+2) Noes But No Long Range D~n(isupporting

confidence: 93%

Structural comparison of a 15 residue peptide from the V3 loop of HIV‐1_IIIb and an O‐glycosylated analogue

et al. 1996

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As part of a program to study the effect of glycosylation on the three-dimensional structures of HIV-ImB V3 peptide constructs, we have examined the solution structures of a 15 residue peptide (RIQRGPGRAFVTIGK, P18ms), originally mapped as an epitope recognized by CD8 + D u class I MHC-restricted murine cytotoxic T-lymphocytes (CTL), and an analogue (P18mB-g), O-glycosylated with an t~-galactosamine on Thr-12, using NMR, circular dichroism and molecular modeling methods. Our studies show that the peptides sample mainly random conformations in aqueous solution near 25°C and become more ordered by the addition of trifluoroethanol. Upon decreasing the temperature to 5°C, a reverse turn is formed around the immunodominant tip (GS-RS). Glycosylation on T Iz 'tightens' the turn slightly as suggested by NOE and CD analysis. In addition, the sugar has a defined conformation with respect to the peptide backbone and influences the local peptide conformation. These data suggest that simple glycosylation may influence the conformational equilibrium of a V3 peptide which contains a domain critical for antibody recognition and virus neutralization. We also show that the ability of cytotoxic Tlymphocytes (CTL) to lyse tumor cells presenting P18ttm was completely abrogated by threonine glycosylation.

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Section: Dnn(ii+l) and Weak Dan(ii+2) Noes But No Long Range D~n(isupporting

confidence: 93%

Structural comparison of a 15 residue peptide from the V3 loop of HIV‐1_IIIb and an O‐glycosylated analogue

et al. 1996

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“…This suggests that the corresponding linear epitope, which was characterized with synthetic peptides (Van der Heijden et al, 1993) also belongs to minor antigenic site c. Therefore the peptide strategy indicates as highly immunodominant a region of the G protein which is only recognized by half of our WB + MAbs, a category which represents only 2% of our MAbs. Should this observation be generalized, it would mean that the peptide approach, although it has been successfully used to map some neutralizing epitopes of viral antigens (Muller et al, 1982;Parry et al, 1989;Rini et al, 1993) is not suitable for the characterization of complex major antigenic sites as those of rabies virus G protein.…”

Section: Discussionmentioning

confidence: 99%

Immunodominant epitopes defined by a yeast-expressed library of random fragments of the rabies virus glycoprotein map outside major antigenic sites

Lafay

Benmansour

Chébli

et al. 1996

Journal of General Virology

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Nineteen yeast colonies secreting rabies virus glycoprotein (G) peptides immunoreactive with polyclonal anti-rabies virus sera were selected from a random expression library. The peptides, around 80 amino acids long, spanned amino acids only recognized by about 1% of our MAbs. Three of these WB + MAbs had significant neutralizing activity; two were used for the selection of antigenic mutants (MAR mutants). Some mutants had a substitution within the region delimited by the peptides, confirming the pertinence of both the peptide and escape mutant approaches. However, a few mutants had a substitution outside the peptide-delimited region, suggesting that remote mutation(s) could affect epitope accessibility in the native protein.

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“…Also, the vicinal JN~ coupling constant for Thr 23 is lower than 6.0 Hz in water. Experimental NMR evidence from previous studies on the complete V3 loops of the MN [23,24], the Chang Mai [25] and the RF (Vranken et al, submitted) strains, and on linear partial V3 loop peptides from the IIIB [39] and the RF [40] strains, as well as X-ray structures of complexes between antibodies and a peptide corresponding to the central region of the V3 loop of the MN strain [41,42] revealed the presence of a tight turn in the conserved GPGR region. The observed NOE contacts for the Consensus V3 loop peptide support this conclusion.…”

Section: Conformation In Watermentioning

confidence: 90%

The complete Consensus V3 loop peptide of the envelope protein gp120 of HIV‐1 shows pronounced helical character in solution

et al. 1995

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The disulfide bridge closed cyclic peptide corresponding to the whole Consensus V3 loop of the envelope protein gpl20 of HIV-1 was examined by proton 2D-NMR spectroscopy in water and in a 20% trifluoroethanol/water solution. In water, NOE data support a B-turn conformation for the central conservative GPGR region and point towards partial formation of a helix in the C-terminal part. Upon addition of trifluoroethanol, a C-terminal helix is formed. This is evidenced by NOE data, a-proton chemical shift changes and changes in the JNo vicinal coupling constants. The C-terminal helix is amphipathic and also occurs in other examined strains. It could therefore be an important feature for the functioning of the V3 loop.

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Crystal structure of a human immunodeficiency virus type 1 neutralizing antibody, 50.1, in complex with its V3 loop peptide antigen.

Cited by 200 publications

References 24 publications

Structural comparison of a 15 residue peptide from the V3 loop of HIV‐1_IIIb and an O‐glycosylated analogue

Structural comparison of a 15 residue peptide from the V3 loop of HIV‐1_IIIb and an O‐glycosylated analogue

Immunodominant epitopes defined by a yeast-expressed library of random fragments of the rabies virus glycoprotein map outside major antigenic sites

The complete Consensus V3 loop peptide of the envelope protein gp120 of HIV‐1 shows pronounced helical character in solution

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Crystal structure of a human immunodeficiency virus type 1 neutralizing antibody, 50.1, in complex with its V3 loop peptide antigen.

Cited by 200 publications

References 24 publications

Structural comparison of a 15 residue peptide from the V3 loop of HIV‐1IIIb and an O‐glycosylated analogue

Structural comparison of a 15 residue peptide from the V3 loop of HIV‐1IIIb and an O‐glycosylated analogue

Immunodominant epitopes defined by a yeast-expressed library of random fragments of the rabies virus glycoprotein map outside major antigenic sites

The complete Consensus V3 loop peptide of the envelope protein gp120 of HIV‐1 shows pronounced helical character in solution

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Product

Resources

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Structural comparison of a 15 residue peptide from the V3 loop of HIV‐1_IIIb and an O‐glycosylated analogue

Structural comparison of a 15 residue peptide from the V3 loop of HIV‐1_IIIb and an O‐glycosylated analogue