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* The Mina and Everard Goodman Faculty of Life Science, Bar Ilan University, Ramat-Gan Israel;
CUBIC, Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032;
Columbia University Center for Computational Biology and Bioinformatics (C2B2), New York, NY 10032; and
NorthEast Structural Genomics Consortium (NESG), Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032
Exact identification of complementarity determining regions (CDRs) is crucial for understanding and manipulating antigenic interactions. One way to do this is by marking residues on the antibody that interact with B cell epitopes on the antigen. This, of course, requires identification of B cell epitopes, which could be done by marking residues on the antigen that bind to CDRs, thus requiring identification of CDRs. To circumvent this vicious circle, existing tools for identifying CDRs are based on sequence analysis or general biophysical principles. Often, these tools, which are based on partial data, fail to agree on the boundaries of the CDRs. Herein we present an automated procedure for identifying CDRs and B cell epitopes using consensus structural regions that interact with the antigens in all known antibody-protein complexes. Consequently, we provide the first comprehensive analysis of all CDR-epitope complexes of known three-dimensional structure. The CDRs we identify only partially overlap with the regions suggested by existing methods. We found that the general physicochemical properties of both CDRs and B cell epitopes are rather peculiar. In particular, only four amino acids account for most of the sequence of CDRs, and several types of amino acids almost never appear in them. The secondary structure content and the conservation of B cell epitopes are found to be different than previously thought. These characteristics of CDRs and epitopes may be instrumental in choosing which residues to mutate in experimental search for epitopes. They may also assist in computational design of antibodies and in predicting B cell epitopes.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by U54-GM074958 granted to the Northeast Structural Genomics consortium from the Protein Structure Initiative of the National Institutes of Health and by R0-GM079767 from the National Institute of General Medical Sciences at the National Institutes of Health.
2 Y.O. and A.S. contributed equally to this study.
3 Address correspondence and reprint requests to Dr. Yanay Ofran, The Mina and Everard Goodman Faculty of Life Science, Bar Ilan University, Ramat-Gan 52900, Israel. E-mail address: yanay{at}ofranlab.org
4 Abbreviations used in this paper: CDR, complementarity determining regions; PDB, Protein Data Bank.
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