Structure-function analysis and insights into the reduced toxicity of Abrus precatorius agglutinin I in relation to abrin

Bagaria, A., Surendranath, K., Ramagopal, U.A., Ramakumar, S. and Karande, A.A. 2006. Structure-function analysis and insights into the reduced toxicity of Abrus precatorius agglutinin I in relation to abrin. Journal of Biological Chemistry . 281, pp. 34465-34474. doi:10.1074/jbc.M601777200

TitleStructure-function analysis and insights into the reduced toxicity of Abrus precatorius agglutinin I in relation to abrin
AuthorsBagaria, A., Surendranath, K., Ramagopal, U.A., Ramakumar, S. and Karande, A.A.
Abstract

Abrin and agglutinin-I from the seeds of Abrus precatorius are type II ribosome-inactivating proteins that inhibit protein synthesis in eukaryotic cells. The two toxins share a high degree of sequence similarity; however, agglutinin-I is weaker in its activity. We compared the kinetics of protein synthesis inhibition by abrin and agglutinin-I in two different cell lines and found that approximately 200-2000-fold higher concentration of agglutinin-I is needed for the same degree of inhibition. Like abrin, agglutinin-I also induced apoptosis in the cells by triggering the intrinsic mitochondrial pathway, although at higher concentrations as compared with abrin. The reason for the decreased toxicity of agglutinin-I became apparent on the analysis of the crystal structure of agglutinin-I obtained by us in comparison with that of the reported structure of abrin. The overall protein folding of agglutinin-I is similar to that of abrin-a with a single disulfide bond holding the toxic A subunit and the lectin-like B-subunit together, constituting a heterodimer. However, there are significant differences in the secondary structural elements, mostly in the A chain. The substitution of Asn-200 in abrin-a with Pro-199 in agglutinin-I seems to be a major cause for the decreased toxicity of agglutinin-I. This perhaps is not a consequence of any kink formation by a proline residue in the helical segment, as reported by others earlier, but due to fewer interactions that proline can possibly have with the bound substrate.

KeywordsAbrin Abrus agglutinin structure function
JournalJournal of Biological Chemistry
Journal citation281, pp. 34465-34474
ISSN0021-9258
Year2006
PublisherAmerican Society for Microbiology and Molecular Biology
Digital Object Identifier (DOI)doi:10.1074/jbc.M601777200
Publication dates
Published2006

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