THE 3-DIMENSIONAL STRUCTURES OF A POLYSACCHARIDE BINDING ANTIBODY TO CRYPTOCOCCUS-NEOFORMANS AND ITS COMPLEX WITH A PEPTIDE FROM A PHAGE DISPLAY LIBRARY - IMPLICATIONS FOR THE IDENTIFICATION OF PEPTIDE MIMOTOPES

The three-dimensional structure of 2H1, a protective monoclonal antibo dy to Cryptococcus neoformans, has been solved at 2.4 Angstrom resolut ion, In both its unbound form and in complex with the 12 amino acid re sidue peptide PAI (GLQYTPSWMLVG). PAI was previously identified a pote ntial mimotope of the cryptococcal capsular polysaccharide by screenin g of a phage display peptide library. Peptide binding is associated wi th only minor rearrangements of some side-chains and a small shift in the H2 loop of the antibody. The peptide assumes a tightly coiled conf ormation consisting of one inverse gamma-turn and one type II beta-tur n that serves to place the entire peptide motif, consisting of Thr(P5) , Pro(P6), Trp(P8), Met(P9) and Leu(P10), into a depression in the ant ibody combining site. A small number of I-I-bonds between peptide and antibody contribute to the affinity and specificity. Poor steric compl ementarity between PA1 and the antibody heavy chain along with the fac t that the majority of the interactions between 2H1 and PA1 involve va n der Waals interactions with the light chain may explain why this pep tide acts as only a partial mimotope of the capsular polysaccharide ep itope, (C) 1997 Academic Press Limited.