Effects of HCDR transplantation on the biochemical properties of diverse antibody active sites
Gulliver, Gene Allen
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https://hdl.handle.net/2142/19828
Description
Title
Effects of HCDR transplantation on the biochemical properties of diverse antibody active sites
Author(s)
Gulliver, Gene Allen
Issue Date
1995
Doctoral Committee Chair(s)
Voss, Edward W., Jr.
Department of Study
Microbiology
Discipline
Microbiology
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Keyword(s)
Biology, Microbiology
Health Sciences, Immunology
Language
eng
Abstract
The diverse active site structures of Map 4-4-20 (pocket; anti-fluorescein) and 04-01(cleft; anti-ssDNA) have been studied extensively (Herron et al., 1989; Denzin et al., 1991; Herron et al., 1991; Denzin et al., 1993; Rumbley et al., 1993), and have led to the hypothesis that the unique biochemical properties exhibited by the active sites of these two antibodies are a function of properties intrinsic to their respective heavy chains, as the light chains are nearly identical, while the heavy chains differ significantly (Bedzyk et al., 1990; Smith et al., 1989; Smith and Voss, 1990). In order to investigate this hypothesis, hybrid single chain antibodies were generated by transplanting heavy chain framework and complementarity determining regions (HFRs and HCDRs) from anti-fluorescein SCA 4-4-20 into the H-chain of anti-ssDNA 04-01 as a means to identify those HFRs and HCDRs required to convey the biochemical properties (structure, function, and stability) of diverse antibody active sites, i.e., a cleft versus a pocket. Such analyses yielded significant information concerning the dependence of antibody active site properties on heavy chain primary structure, which could be applied to other systems to aid in the understanding of the relationships between primary structure and the various biochemical properties exhibited by a protein.
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