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Article: Crystal Structure of the Broadly Cross-Reactive HIV-1-Neutralizing Fab X5 and Fine Mapping of Its Epitope
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TitleCrystal Structure of the Broadly Cross-Reactive HIV-1-Neutralizing Fab X5 and Fine Mapping of Its Epitope
 
AuthorsDarbha, R1
Phogat, S1
Labrijn, AF2
Shu, Y1
Gu, Y1
Andrykovitch, M1
Zhang, MY1
Pantophlet, R2
Martin, L3
Vita, C3
Burton, DR2
Dimitrov, DS1
Ji, X1
 
Issue Date2004
 
PublisherAmerican Chemical Society. The Journal's web site is located at http://pubs.acs.org/biochemistry
 
CitationBiochemistry, 2004, v. 43 n. 6, p. 1410-1417 [How to Cite?]
DOI: http://dx.doi.org/10.1021/bi035323x
 
AbstractThe human monoclonal antibody Fab X5 neutralizes a broad range of HIV-1 primary isolates. The crystal structure of X5 has been determined at 1.9 Å resolution. There are two crystallographically independent Fab fragments in the asymmetric unit. The crystallographic R value for the final model is 0.22. The antibody-combining site features a long (22 amino acid residues) CDR H3 with a protruding hook-shaped motif. The X5 structure and site-directed mutagenesis data suggest that X5 amino acid residues W100 and Y100F in the CDR H3 motif may be critical for the binding of Fab X5 to gp120. X5 bound to a complex of a CD4 mimetic and gp120 with approximately the same kinetics and affinity as to a CD4-gp120 complex, suggesting that specific interactions between CD4 and X5 are unlikely to contribute to the binding of X5 to gp120-CD4 complexes. Binding of X5 to alanine scanning mutants of gp120JR-CSF complexed with CD4 suggested a critical role of the highly conserved amino acid residues at positions 423 and 432. The X5 structure and fine mapping of its epitope may assist in the elucidation of the mechanisms of viral entry and neutralization, and the development of HIV-1 inhibitors and vaccines.
 
ISSN0006-2960
2013 Impact Factor: 3.194
 
DOIhttp://dx.doi.org/10.1021/bi035323x
 
ISI Accession Number IDWOS:000188928500002
 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorDarbha, R
 
dc.contributor.authorPhogat, S
 
dc.contributor.authorLabrijn, AF
 
dc.contributor.authorShu, Y
 
dc.contributor.authorGu, Y
 
dc.contributor.authorAndrykovitch, M
 
dc.contributor.authorZhang, MY
 
dc.contributor.authorPantophlet, R
 
dc.contributor.authorMartin, L
 
dc.contributor.authorVita, C
 
dc.contributor.authorBurton, DR
 
dc.contributor.authorDimitrov, DS
 
dc.contributor.authorJi, X
 
dc.date.accessioned2012-08-08T08:49:31Z
 
dc.date.available2012-08-08T08:49:31Z
 
dc.date.issued2004
 
dc.description.abstractThe human monoclonal antibody Fab X5 neutralizes a broad range of HIV-1 primary isolates. The crystal structure of X5 has been determined at 1.9 Å resolution. There are two crystallographically independent Fab fragments in the asymmetric unit. The crystallographic R value for the final model is 0.22. The antibody-combining site features a long (22 amino acid residues) CDR H3 with a protruding hook-shaped motif. The X5 structure and site-directed mutagenesis data suggest that X5 amino acid residues W100 and Y100F in the CDR H3 motif may be critical for the binding of Fab X5 to gp120. X5 bound to a complex of a CD4 mimetic and gp120 with approximately the same kinetics and affinity as to a CD4-gp120 complex, suggesting that specific interactions between CD4 and X5 are unlikely to contribute to the binding of X5 to gp120-CD4 complexes. Binding of X5 to alanine scanning mutants of gp120JR-CSF complexed with CD4 suggested a critical role of the highly conserved amino acid residues at positions 423 and 432. The X5 structure and fine mapping of its epitope may assist in the elucidation of the mechanisms of viral entry and neutralization, and the development of HIV-1 inhibitors and vaccines.
 
dc.description.natureLink_to_subscribed_fulltext
 
dc.identifier.citationBiochemistry, 2004, v. 43 n. 6, p. 1410-1417 [How to Cite?]
DOI: http://dx.doi.org/10.1021/bi035323x
 
dc.identifier.doihttp://dx.doi.org/10.1021/bi035323x
 
dc.identifier.epage1417
 
dc.identifier.isiWOS:000188928500002
 
dc.identifier.issn0006-2960
2013 Impact Factor: 3.194
 
dc.identifier.issue6
 
dc.identifier.pmid14769016
 
dc.identifier.scopuseid_2-s2.0-10744224411
 
dc.identifier.spage1410
 
dc.identifier.urihttp://hdl.handle.net/10722/157384
 
dc.identifier.volume43
 
dc.languageeng
 
dc.publisherAmerican Chemical Society. The Journal's web site is located at http://pubs.acs.org/biochemistry
 
dc.publisher.placeUnited States
 
dc.relation.ispartofBiochemistry
 
dc.relation.referencesReferences in Scopus
 
dc.subject.meshAntibodies, Monoclonal - Chemistry - Genetics - Metabolism
 
dc.subject.meshAntigens, Cd4 - Chemistry - Immunology - Metabolism
 
dc.subject.meshAntiviral Agents - Chemistry - Genetics - Metabolism
 
dc.subject.meshBinding Sites - Genetics
 
dc.subject.meshCross Reactions - Genetics
 
dc.subject.meshCrystallization
 
dc.subject.meshCrystallography, X-Ray
 
dc.subject.meshEpitopes - Chemistry - Immunology - Metabolism
 
dc.subject.meshHiv Envelope Protein Gp120 - Chemistry - Genetics - Metabolism
 
dc.subject.meshHiv-1 - Immunology - Pathogenicity
 
dc.subject.meshHumans
 
dc.subject.meshImmunoglobulin Fab Fragments - Chemistry - Genetics - Metabolism
 
dc.subject.meshModels, Molecular
 
dc.subject.meshMutagenesis, Site-Directed
 
dc.subject.meshNeutralization Tests
 
dc.subject.meshPeptide Mapping - Methods
 
dc.subject.meshProtein Structure, Tertiary - Genetics
 
dc.subject.meshSurface Plasmon Resonance
 
dc.titleCrystal Structure of the Broadly Cross-Reactive HIV-1-Neutralizing Fab X5 and Fine Mapping of Its Epitope
 
dc.typeArticle
 
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<contributor.author>Shu, Y</contributor.author>
<contributor.author>Gu, Y</contributor.author>
<contributor.author>Andrykovitch, M</contributor.author>
<contributor.author>Zhang, MY</contributor.author>
<contributor.author>Pantophlet, R</contributor.author>
<contributor.author>Martin, L</contributor.author>
<contributor.author>Vita, C</contributor.author>
<contributor.author>Burton, DR</contributor.author>
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<subject.mesh>Antigens, Cd4 - Chemistry - Immunology - Metabolism</subject.mesh>
<subject.mesh>Antiviral Agents - Chemistry - Genetics - Metabolism</subject.mesh>
<subject.mesh>Binding Sites - Genetics</subject.mesh>
<subject.mesh>Cross Reactions - Genetics</subject.mesh>
<subject.mesh>Crystallization</subject.mesh>
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<subject.mesh>Hiv Envelope Protein Gp120 - Chemistry - Genetics - Metabolism</subject.mesh>
<subject.mesh>Hiv-1 - Immunology - Pathogenicity</subject.mesh>
<subject.mesh>Humans</subject.mesh>
<subject.mesh>Immunoglobulin Fab Fragments - Chemistry - Genetics - Metabolism</subject.mesh>
<subject.mesh>Models, Molecular</subject.mesh>
<subject.mesh>Mutagenesis, Site-Directed</subject.mesh>
<subject.mesh>Neutralization Tests</subject.mesh>
<subject.mesh>Peptide Mapping - Methods</subject.mesh>
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Author Affiliations
  1. National Cancer Institute at Frederick
  2. Scripps Research Institute
  3. CEA Saclay