1t6b
From Proteopedia
(New page: 200px<br /> <applet load="1t6b" size="450" color="white" frame="true" align="right" spinBox="true" caption="1t6b, resolution 2.50Å" /> '''Crystal structure o...) |
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| - | [[Image:1t6b.gif|left|200px]]<br /> | + | [[Image:1t6b.gif|left|200px]]<br /><applet load="1t6b" size="350" color="white" frame="true" align="right" spinBox="true" |
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caption="1t6b, resolution 2.50Å" /> | caption="1t6b, resolution 2.50Å" /> | ||
'''Crystal structure of B. anthracis Protective Antigen complexed with human Anthrax toxin receptor'''<br /> | '''Crystal structure of B. anthracis Protective Antigen complexed with human Anthrax toxin receptor'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Anthrax toxin consists of the proteins protective antigen (PA), lethal | + | Anthrax toxin consists of the proteins protective antigen (PA), lethal factor (LF) and oedema factor (EF). The first step of toxin entry into host cells is the recognition by PA of a receptor on the surface of the target cell. Subsequent cleavage of receptor-bound PA enables EF and LF to bind and form a heptameric PA63 pre-pore, which triggers endocytosis. Upon acidification of the endosome, PA63 forms a pore that inserts into the membrane and translocates EF and LF into the cytosol. Two closely related host cell receptors, TEM8 and CMG2, have been identified. Both bind to PA with high affinity and are capable of mediating toxicity. Here, we report the crystal structure of the PA-CMG2 complex at 2.5 A resolution. The structure reveals an extensive receptor-pathogen interaction surface mimicking the non-pathogenic recognition of the extracellular matrix by integrins. The binding surface is closely conserved in the two receptors and across species, but is quite different in the integrin domains, explaining the specificity of the interaction. CMG2 engages two domains of PA, and modelling of the receptor-bound PA63 heptamer suggests that the receptor acts as a pH-sensitive brace to ensure accurate and timely membrane insertion. The structure provides new leads for the discovery of anthrax anti-toxins, and should aid the design of cancer therapeutics. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1T6B is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Bacillus_anthracis Bacillus anthracis] and [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with CA, MN, NA and PG4 as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 1T6B is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Bacillus_anthracis Bacillus anthracis] and [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=CA:'>CA</scene>, <scene name='pdbligand=MN:'>MN</scene>, <scene name='pdbligand=NA:'>NA</scene> and <scene name='pdbligand=PG4:'>PG4</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1T6B OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
| - | [[Category: Bankston, L | + | [[Category: Bankston, L A.]] |
| - | [[Category: Leppla, S | + | [[Category: Leppla, S H.]] |
| - | [[Category: Liddington, R | + | [[Category: Liddington, R C.]] |
[[Category: Santelli, E.]] | [[Category: Santelli, E.]] | ||
[[Category: CA]] | [[Category: CA]] | ||
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[[Category: bacillus anthracis; anthrax toxin; x-ray crystallography]] | [[Category: bacillus anthracis; anthrax toxin; x-ray crystallography]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:10:21 2008'' |
Revision as of 13:10, 21 February 2008
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Crystal structure of B. anthracis Protective Antigen complexed with human Anthrax toxin receptor
Contents |
Overview
Anthrax toxin consists of the proteins protective antigen (PA), lethal factor (LF) and oedema factor (EF). The first step of toxin entry into host cells is the recognition by PA of a receptor on the surface of the target cell. Subsequent cleavage of receptor-bound PA enables EF and LF to bind and form a heptameric PA63 pre-pore, which triggers endocytosis. Upon acidification of the endosome, PA63 forms a pore that inserts into the membrane and translocates EF and LF into the cytosol. Two closely related host cell receptors, TEM8 and CMG2, have been identified. Both bind to PA with high affinity and are capable of mediating toxicity. Here, we report the crystal structure of the PA-CMG2 complex at 2.5 A resolution. The structure reveals an extensive receptor-pathogen interaction surface mimicking the non-pathogenic recognition of the extracellular matrix by integrins. The binding surface is closely conserved in the two receptors and across species, but is quite different in the integrin domains, explaining the specificity of the interaction. CMG2 engages two domains of PA, and modelling of the receptor-bound PA63 heptamer suggests that the receptor acts as a pH-sensitive brace to ensure accurate and timely membrane insertion. The structure provides new leads for the discovery of anthrax anti-toxins, and should aid the design of cancer therapeutics.
Disease
Known diseases associated with this structure: Fibromatosis, juvenile hyaline OMIM:[608041], Hyalinosis, infantile systemic OMIM:[608041]
About this Structure
1T6B is a Protein complex structure of sequences from Bacillus anthracis and Homo sapiens with , , and as ligands. Full crystallographic information is available from OCA.
Reference
Crystal structure of a complex between anthrax toxin and its host cell receptor., Santelli E, Bankston LA, Leppla SH, Liddington RC, Nature. 2004 Aug 19;430(7002):905-8. Epub 2004 Jul 4. PMID:15243628
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