1mdt
From Proteopedia
(New page: 200px<br /> <applet load="1mdt" size="450" color="white" frame="true" align="right" spinBox="true" caption="1mdt, resolution 2.3Å" /> '''THE REFINED STRUCTUR...) |
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| - | [[Image:1mdt.gif|left|200px]]<br /> | + | [[Image:1mdt.gif|left|200px]]<br /><applet load="1mdt" size="350" color="white" frame="true" align="right" spinBox="true" |
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caption="1mdt, resolution 2.3Å" /> | caption="1mdt, resolution 2.3Å" /> | ||
'''THE REFINED STRUCTURE OF MONOMERIC DIPHTHERIA TOXIN AT 2.3 ANGSTROMS RESOLUTION'''<br /> | '''THE REFINED STRUCTURE OF MONOMERIC DIPHTHERIA TOXIN AT 2.3 ANGSTROMS RESOLUTION'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The structure of toxic monomeric diphtheria toxin (DT) was determined at | + | 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== | ==About this Structure== | ||
| - | 1MDT is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Corynephage_beta Corynephage beta] with APU as [http://en.wikipedia.org/wiki/ligand ligand]. The following page contains interesting information on the relation of 1MDT with [[http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/pdb69_1.html Cholera Toxin]]. Full crystallographic information is available from [http:// | + | 1MDT is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Corynephage_beta Corynephage beta] with <scene name='pdbligand=APU:'>APU</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. The following page contains interesting information on the relation of 1MDT with [[http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/pdb69_1.html Cholera Toxin]]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1MDT OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Corynephage beta]] | [[Category: Corynephage beta]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Bennett, M | + | [[Category: Bennett, M J.]] |
[[Category: Eisenberg, D.]] | [[Category: Eisenberg, D.]] | ||
[[Category: APU]] | [[Category: APU]] | ||
[[Category: toxin]] | [[Category: toxin]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:54:14 2008'' |
Revision as of 11:54, 21 February 2008
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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 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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