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Crystal structure to 2.45 Å resolution of a monoclonal Fab specific for the Brucella A cell wall polysaccharide antigen
Author(s) -
Rose D. R.,
Przybylska M.,
To R. J.,
Kayden C. S.,
Vorberg E.,
Young N. M.,
Bundle D. R.,
Oomen R. P.
Publication year - 1993
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1002/pro.5560020705
Subject(s) - antigen , immunoglobulin fab fragments , chemistry , antibody , monoclonal antibody , immunoglobulin light chain , binding site , brucella , biology , microbiology and biotechnology , biochemistry , complementarity determining region , genetics , virology , brucellosis
The atomic structure of an antibody antigen‐binding fragment (Fab) at 2.45Åresolution shows that polysaccharide antigen conformation and Fab structure dictated by combinatorial diversity and domain association are responsible for the fine specificity of the Brucella ‐specific antibody, YsT9.1. It discriminates the Brucella abortus A antigen from the nearly identical Brucella melitensis M antigen by forming a groove‐type binding site, lined with tyrosine residues, that accommodates the rodlike A antigen but excludes the kinked structure of the M antigen, as envisioned by a model of the antigen built into the combining site. The variable‐heavy (V H ) and variable‐light (V L ) domains are derived from genes closely related to two used in previously solved structures, M603 and R19.9, respectively. These genes combine in YsT9.1 to form an antibody of totally different specificity. Comparison of this X‐ray structure with a previously built model of the YsT9.1 combining site based on these homologies highlights the importance of V L :V H association as a determinant of specificity and suggests that small changes at the V L :V H interface, unanticipated in modeling, may cause significant modulation of binding‐site properties.