Determination of the Structural Basis of Antibody Diversity Using NMR

Abstract

We have constructed semiempirical/semitheoretical 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.

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Document Details

Document Type
Technical Report
Publication Date
Jun 15, 1989
Accession Number
ADA209373

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  • Harden M. Mcconnell

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  • Stanford University

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  • Amines
  • Amino Acids
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