ARE "HOT SPOTS" [SUPER-FLEXIBLE REGIONS] ON THE SURFACE OF AN ANTIGEN ESSENTIAL FOR ANTIGEN-ANTIBODY BINDING? Gerson H Cohen, David R Davies, National Institutes of Health, NIDDK/LMB, Bethesda, MD 20892 USA

The lysozyme molecule has been studied crystallographically in complex with a number of Fv and Fab antibody fragments. In these complexes the structure of the lysozyme molecule shows significant changes at one or more of three points in its sequence. The Ca positions at residues 47, 70-71 and 101-103 of lysozyme in one complex differ from the corresponding position in a second by 1-2 A on the average and by as much as 7 A. The average general difference in Ca positions is 0.5-0.75 A. This main chain flexibility demonstrated by bound lysozyme is found in the published structures of native unbound lysozyme and is not merely a distortion resulting from the association with antibody fragments. In all of the complexes reported at least one of these three regions is partially buried as a result of complex formation. In an attempt to determine whether this flexibility is required for antibody binding or is merely coincidental, we examined neuraminidase and its complexes with NC41 and NC10. The neuraminidase structures do not exhibit the flexibility shown by lysozyme; the maximum difference noted in the comparison of the neuraminidases is only 1A. Neuraminidase does not support the requirement of hot spots in the antigen-antibody interface.

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