Antibody and antigen contact residues define epitope and paratope size and structure.
نویسندگان
چکیده
A total of 111 Ag-Ab x-ray crystal structures of large protein Ag epitopes and paratopes were analyzed to inform the process of eliciting or selecting functional and therapeutic Abs. These analyses illustrate that Ab contact residues (CR) are distributed in three prominent CR regions (CRR) on L and H chains that overlap but do not coincide with Ab CDR. The number of Ag and Ab CRs per structure are overlapping and centered around 18 and 19, respectively. The CR span (CRS), a novel measure introduced in this article, is defined as the minimum contiguous amino acid sequence containing all CRs of an Ag or Ab and represents the size of a complete structural epitope or paratope, inclusive of CR and the minimum set of supporting residues required for proper conformation. The most frequent size of epitope CRS is 50-79 aa, which is similar in size to L (60-69) and H chain (70-79) CRS. The size distribution of epitope CRS analyzed in this study ranges from ~20 to 400 aa, similar to the distribution of independent protein domain sizes reported in the literature. Together, the number of CRs and the size of the CRS demonstrate that, on average, complete structural epitopes and paratopes are equal in size to each other and similar in size to intact protein domains. Thus, independent protein domains inclusive of biologically relevant sites represent the fundamental structural unit bound by, and useful for eliciting or selecting, functional and therapeutic Abs.
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عنوان ژورنال:
- Journal of immunology
دوره 191 3 شماره
صفحات -
تاریخ انتشار 2013