2gww
From Proteopedia
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|ACTIVITY= | |ACTIVITY= | ||
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[1rkc|1RKC]], [[1rke|1RKE]], [[1ydi|1YDI]], [[1syq|1SYQ]], [[1tr2|1TR2]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2gww FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2gww OCA], [http://www.ebi.ac.uk/pdbsum/2gww PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2gww RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==Overview== | ||
Shigella flexneri, the causative agent of bacillary dysentery, injects invasin proteins through a type III secretion apparatus upon contacting the host cell, which triggers pathogen internalization. The invasin IpaA is essential for S. flexneri pathogenesis and binds to the cytoskeletal protein vinculin to facilitate host cell entry. We report that IpaA harbors two vinculin-binding sites (VBSs) within its C-terminal domain that bind to and activate vinculin in a mutually exclusive fashion. Only the highest affinity C-terminal IpaA VBS is necessary for efficient entry and cell-cell spread of S. flexneri, whereas the lower affinity VBS appears to contribute to vinculin recruitment at entry foci of the pathogen. Finally, the crystal structures of vinculin in complex with the VBSs of IpaA reveal the mechanism by which IpaA subverts vinculin's functions, where S. flexneri utilizes a remarkable level of molecular mimicry of the talin-vinculin interaction to activate vinculin. Mimicry of vinculin's interactions may therefore be a general mechanism applied by pathogens to infect the host cell. | Shigella flexneri, the causative agent of bacillary dysentery, injects invasin proteins through a type III secretion apparatus upon contacting the host cell, which triggers pathogen internalization. The invasin IpaA is essential for S. flexneri pathogenesis and binds to the cytoskeletal protein vinculin to facilitate host cell entry. We report that IpaA harbors two vinculin-binding sites (VBSs) within its C-terminal domain that bind to and activate vinculin in a mutually exclusive fashion. Only the highest affinity C-terminal IpaA VBS is necessary for efficient entry and cell-cell spread of S. flexneri, whereas the lower affinity VBS appears to contribute to vinculin recruitment at entry foci of the pathogen. Finally, the crystal structures of vinculin in complex with the VBSs of IpaA reveal the mechanism by which IpaA subverts vinculin's functions, where S. flexneri utilizes a remarkable level of molecular mimicry of the talin-vinculin interaction to activate vinculin. Mimicry of vinculin's interactions may therefore be a general mechanism applied by pathogens to infect the host cell. | ||
| - | |||
| - | ==Disease== | ||
| - | Known disease associated with this structure: Cardiomyopathy, dilated, 1W OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=193065 193065]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: protein complex]] | [[Category: protein complex]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 03:22:43 2008'' |
Revision as of 00:22, 31 March 2008
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| , resolution 2.72Å | |||||||
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| Related: | 1RKC, 1RKE, 1YDI, 1SYQ, 1TR2
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Human vinculin (head domain, Vh1, residues 1-258) in complex with Shigella's IpaA vinculin binding site (residues 602-633)
Overview
Shigella flexneri, the causative agent of bacillary dysentery, injects invasin proteins through a type III secretion apparatus upon contacting the host cell, which triggers pathogen internalization. The invasin IpaA is essential for S. flexneri pathogenesis and binds to the cytoskeletal protein vinculin to facilitate host cell entry. We report that IpaA harbors two vinculin-binding sites (VBSs) within its C-terminal domain that bind to and activate vinculin in a mutually exclusive fashion. Only the highest affinity C-terminal IpaA VBS is necessary for efficient entry and cell-cell spread of S. flexneri, whereas the lower affinity VBS appears to contribute to vinculin recruitment at entry foci of the pathogen. Finally, the crystal structures of vinculin in complex with the VBSs of IpaA reveal the mechanism by which IpaA subverts vinculin's functions, where S. flexneri utilizes a remarkable level of molecular mimicry of the talin-vinculin interaction to activate vinculin. Mimicry of vinculin's interactions may therefore be a general mechanism applied by pathogens to infect the host cell.
About this Structure
2GWW is a Protein complex structure of sequences from Homo sapiens and Shigella flexneri. Full crystallographic information is available from OCA.
Reference
Shigella applies molecular mimicry to subvert vinculin and invade host cells., Izard T, Tran Van Nhieu G, Bois PR, J Cell Biol. 2006 Nov 6;175(3):465-75. PMID:17088427
Page seeded by OCA on Mon Mar 31 03:22:43 2008
