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 pepti de to mimic the structure of the protein surface, the peptide has been studied by NMR in aqueous solution as well as under denaturing condit ions. The peptide is shown to be a random coil in solution. However, t he sequence forming a 3(10)helix in the complex is biased into a helic al conformation according to NOE intensity data as well as from urea a nd pH titrations. This sequence adopts the same conformation in an unr elated protein. NOE data suggest that a beta- turn found in the comple x may be sampled in solution. Also, Glu4, interacting with Arg6 in the crystal, has a reduced pK(a) value in solution. It is concluded that the local structure present in the random coil state of VP2(156-170) c ontains enough information to direct the production of antibodies that bind to and neutralize HRV2. (C) 1998 European Peptide Society and Jo hn Wiley & Sons, Ltd.