1mdt

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spinqualitylabelsall models 1mdt, resolution 2.3Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

THE REFINED STRUCTURE OF MONOMERIC DIPHTHERIA TOXIN AT 2.3 ANGSTROMS RESOLUTION

Overview

The structure of toxic monomeric diphtheria toxin (DT) was determined at, 2.3 A resolution by molecular replacement based on the domain structures, in dimeric DT and refined to an R factor of 20.7%. The model consists of 2, monomers in the asymmetric unit (1,046 amino acid residues), including 2, bound adenylyl 3'-5' uridine 3' monophosphate molecules and 396 water, molecules. The structures of the 3 domains are virtually identical in, monomeric and dimeric DT; however, monomeric DT is compact and globular as, compared to the "open" monomer within dimeric DT (Bennett MJ, Choe S, Eisenberg D, 1994b, Protein Sci 3:0000-0000). Detailed differences between, monomeric and dimeric DT are described, particularly (1) changes in, main-chain conformations of 8 residues acting as a hinge to "open" or, "close" the receptor-binding (R) domain, and (2) a possible, receptor-docking site, a beta-hairpin loop protruding from the R domain, containing residues that bind the cell-surface DT receptor. Based on the, monomeric and dimeric DT crystal structures we have determined and the, solution studies of others, we present a 5-step structure-based mechanism, of intoxication: (1) proteolysis of a disulfide-linked surface loop, (residues 186-201) between the catalytic (C) and transmembrane (T), domains; (2) binding of a beta-hairpin loop protruding from the R domain, to the DT receptor, leading to receptor-mediated endocytosis; (3) low, pH-triggered open monomer formation and exposure of apolar surfaces in the, T domain, which insert into the endosomal membrane; (4) translocation of, the C domain into the cytosol; and (5) catalysis by the C domain of, ADP-ribosylation of elongation factor 2.

About this Structure

1MDT is a Single protein structure of sequence from Corynephage beta with APU as ligand. The following page contains interesting information on the relation of 1MDT with [Cholera Toxin]. Full crystallographic information is available from OCA.

Reference

Refined structure of monomeric diphtheria toxin at 2.3 A resolution., Bennett MJ, Eisenberg D, Protein Sci. 1994 Sep;3(9):1464-75. PMID:7833808

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