Analysis of antibodies of known structure suggests a lack of correspondence between the residues in contact with the antigen and those modified by somatic hypermutation

Citation
Md. Ramirez-benitez et Jc. Almagro, Analysis of antibodies of known structure suggests a lack of correspondence between the residues in contact with the antigen and those modified by somatic hypermutation, PROTEINS, 45(3), 2001, pp. 199-206
Citations number
39
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biochemistry & Biophysics
Journal title
PROTEINS-STRUCTURE FUNCTION AND GENETICS
ISSN journal
0887-3585 → ACNP
Volume
45
Issue
3
Year of publication
2001
Pages
199 - 206
Database
ISI
SICI code
0887-3585(20011115)45:3<199:AOAOKS>2.0.ZU;2-Q
Abstract
Forty unique murine antibody-antigen complexes determined at 2.5 Angstrom o r less resolution are analyzed to determine whether the residues in direct contact with the antigen are modified by somatic hypermutation. This was do ne by taking advantage of the recent characterization of the pool of V-K ge rmline genes of the mouse. The average number of residues in contact with t he antigen in the V-L gene, which contains the CDRL-1, CDRL-2, and all but one residue of CDRL-3, was six. The average number of somatic mutations was similar (around five). However, as many as 53% of the antibodies did not s how somatic replacements of residues in contact with the antigen. Another 2 8% had only one. Overall, the frequency of antibodies with increasing numbe r of somatic replacements in residues in contact with the antigen decreased exponentially. A possible explanation of this finding is that mutations in the contacting residues have an adverse effect on the antigen-antibody int eraction. This implies that most of the observed mutations are those remain ing after negative (purifying) selection. Therefore, efficient strategies o f site-directed mutagenesis to improve the affinity of antibodies should be focused on residues other than those directly interacting with the antigen . (C) 2001Wiley-Liss,Inc.