Abteilung Strukturforschung, Max-Planck Institut fur Biochemie, Martinsried, Germany.
e-mail: steipe@lmb.uni-muenchen.de
J Mol Biol 240: 188-192 (1994)
Abstract:
Immunoglobulin variable domains are generally thought of as well
conserved platforms providing the base for antigen binding loops of
highly varying sequence and structure. However, domain evolution must
ensure a balance between optimizing antigen affinity and the
requirements of a stable, cooperatively folding domain. Since random
mutations can carry a significant penalty for domain stability,
constraints are imposed both on the repertoire of germline sequences and
on somatic amino acid replacements during affinity maturation.
Analyzing these constraints in the conceptual framework of statistical
mechanics, we have been able to predict stabilizing mutations in the
McPC603 V kappa domain from sequence information alone with better than
60% success rate. The validity of this concept not only has far reaching
implications for antibody engineering but may also be generalized to
engineer other proteins for higher stability.
Mesh Headings
Unique Identifier: 94300596
Chemical Identifiers (Names)