Computational design of protein antigens that interact with the CDR H3 loop of HIV broadly neutralizing antibody 2F5
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چکیده
منابع مشابه
Structure-guided Alterations of the gp41-directed HIV-1 Broadly Neutralizing Antibody 2F5 Reveal New Properties Regarding its Neutralizing Function
The broadly neutralizing HIV-1 antibody 2F5 recognizes an epitope in the gp41 membrane proximal external region (MPER). The MPER adopts a helical conformation as free peptide, as post-fusogenic forms of gp41, and when bound to the 4E10 monoclonal antibody (Mab). However, when bound to 2F5, the epitope is an extended-loop. The antibody-peptide structure reveals binding between the heavy and ligh...
متن کاملAblation of the complementarity-determining region H3 apex of the anti-HIV-1 broadly neutralizing antibody 2F5 abrogates neutralizing capacity without affecting core epitope binding.
The identification and characterization of broadly neutralizing antibodies (bnAbs) against HIV-1 has formed a major research focus, with the ultimate goal to help in the design of an effective AIDS vaccine. One of these bnAbs, 2F5, has been extensively characterized, and residues at the apex of its unusually long complementarity-determining region (CDR) H3 loop have been shown to be crucial for...
متن کاملRevisiting antibody modeling assessment for CDR-H3 loop
The antigen-binding site of antibodies, also known as complementarity-determining region (CDR), has hypervariable sequence properties. In particular, the third CDR loop of the heavy chain, CDR-H3, has such variability in its sequence, length, and conformation that ordinary modeling techniques cannot build a high-quality structure. At Stage 2 of the Second Antibody Modeling Assessment (AMA-II) h...
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In an attempt to design immunogens that elicit broadly HIV-neutralizing antibodies, we recently engineered monomeric HIV-1 gp120 to bind preferentially b12, a broadly neutralizing antibody to the CD4-binding site (CD4bs) on gp120, by mutating four central residues in the CD4bs to alanine and introducing extra N-glycosylation sites potentially to mask unwanted B-cell epitopes. Despite the favora...
متن کاملIdentification of autoantigens recognized by the 2F5 and 4E10 broadly neutralizing HIV-1 antibodies
Many human monoclonal antibodies that neutralize multiple clades of HIV-1 are polyreactive and bind avidly to mammalian autoantigens. Indeed, the generation of neutralizing antibodies to the 2F5 and 4E10 epitopes of HIV-1 gp41 in man may be proscribed by immune tolerance because mice expressing the V(H) and V(L) regions of 2F5 have a block in B cell development that is characteristic of central...
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ژورنال
عنوان ژورنال: Proteins: Structure, Function, and Bioinformatics
سال: 2014
ISSN: 0887-3585
DOI: 10.1002/prot.24641