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2k42
From Proteopedia
| 2k42, 20 NMR models () | |||||||||
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| Gene: | WAS, IMD2 (Homo sapiens), tccP, ECs2715 (Escherichia coli O157:H7) | ||||||||
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||
Solution Structure of the GTPase Binding Domain of WASP in Complex with EspFU, an EHEC Effector
During infection, enterohaemorrhagic Escherichia coli (EHEC) takes over the actin cytoskeleton of eukaryotic cells by injecting the EspF(U) protein into the host cytoplasm. EspF(U) controls actin by activating members of the Wiskott-Aldrich syndrome protein (WASP) family. Here we show that EspF(U) binds to the autoinhibitory GTPase binding domain (GBD) in WASP proteins and displaces it from the activity-bearing VCA domain (for verprolin homology, central hydrophobic and acidic regions). This interaction potently activates WASP and neural (N)-WASP in vitro and induces localized actin assembly in cells. In the solution structure of the GBD-EspF(U) complex, EspF(U) forms an amphipathic helix that binds the GBD, mimicking interactions of the VCA domain in autoinhibited WASP. Thus, EspF(U) activates WASP by competing directly for the VCA binding site on the GBD. This mechanism is distinct from that used by the eukaryotic activators Cdc42 and SH2 domains, which globally destabilize the GBD fold to release the VCA. Such diversity of mechanism in WASP proteins is distinct from other multimodular systems, and may result from the intrinsically unstructured nature of the isolated GBD and VCA elements. The structural incompatibility of the GBD complexes with EspF(U) and Cdc42/SH2, plus high-affinity EspF(U) binding, enable EHEC to hijack the eukaryotic cytoskeletal machinery effectively.
Structural mechanism of WASP activation by the enterohaemorrhagic E. coli effector EspF(U)., Cheng HC, Skehan BM, Campellone KG, Leong JM, Rosen MK, Nature. 2008 Aug 21;454(7207):1009-13. Epub 2008 Jul 23. PMID:18650809
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
About this Structure
2K42 is a 2 chains structure of sequences from Escherichia coli o157:h7 and Homo sapiens. Full experimental information is available from OCA.
Reference
- Cheng HC, Skehan BM, Campellone KG, Leong JM, Rosen MK. Structural mechanism of WASP activation by the enterohaemorrhagic E. coli effector EspF(U). Nature. 2008 Aug 21;454(7207):1009-13. Epub 2008 Jul 23. PMID:18650809 doi:10.1038/nature07160
Page seeded by OCA on Mon Feb 16 11:41:39 2009
