Determination of the Structural Basis of Antibody Diversity Using NMR
Annual rept. Jul 1988-Jul 1989
STANFORD UNIV CA
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We have constructed semiempiricalsemitheoretical structural models of the twelve anti-nitroxide spin label antibodies previously sequenced in this laboratory. These models are in striking qualitative accord with the NMR difference spectra in showing the presence of a large number of aromatic amino acids especially tyrosines in the combining site region, i.e., within about 20 A of the unpaired electron. The high motional freedom of the tyrosine residues i.e., approx. 10-12 residues in AN01-AN03 inferred from the NMR indicates that these residues play no significant role in maintaining a rigid three-dimensional structure of these proteins. We have determined the germline sequences of AN02 and AN07 and find similar numbers of tyrosine residues in the combining site regions. It is likely that the tyrosine and other residues in the combining site regions that are highly mobile, and distributed over a large surface approx. 20 A x 20A are mostly designed for protein antigen recognition not small haptens including idiotype-anti-idiotype regulation.
- Organic Chemistry