Solution conformation of an immunogenic peptide from HRV2: comparison with the conformation found in a complex with a Fab fragment of an anti-HRV2 neutralizing antibody.
The conformation of a [15]-peptide (H-VKAETRLNPDLQPTE-NH2) from VP2 of rhinovirus HRV2 complexed with a Fab fragment was previously shown by X-ray crystallographic studies to be similar to the one found in the corresponding region of HRV1A. Antibodies raised against this peptide bind to and neutralize HRV2. In order to identify structural features preserved in solution that may explain the ability of this short peptide to mimic the structure of the protein surface, the peptide has been studied by NMR in aqueous solution as well as under denaturing conditions. The peptide is shown to be a random coil in solution. However, the sequence forming a 3(10)helix in the complex is biased into a helical conformation according to NOE intensity data as well as from urea and pH titrations. This sequence adopts the same conformation in an unrelated protein. NOE data suggest that a beta-turn found in the complex may be sampled in solution. Also, Glu4, interacting with Arg6 in the crystal, has a reduced pKa value in solution. It is concluded that the local structure present in the random coil state of VP2(156-170) contains enough information to direct the production of antibodies that bind to and neutralize HRV2.
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Department de Química Orgànica, Universitat de Barcelona, Spain.
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D000595:Amino Acid Sequence; D000906:Antibodies / Q000276:immunology / Q000378:metabolism; D000956:Antigens, Viral / Q000737:chemistry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007140:Immunoglobulin Fab Fragments / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry*; D017510:Protein Folding; D017433:Protein Structure, Secondary; D012229:Rhinovirus / Q000737:chemistry* / Q000276:immunology; D014612:Vaccines / Q000276:immunology; D014764:Viral Proteins / Q000737:chemistry*
D000906:Antibodies; D000956:Antigens, Viral; D007140:Immunoglobulin Fab Fragments; D010446:Peptide Fragments; D014612:Vaccines; D014764:Viral Proteins