2o02
From Proteopedia
(New page: 200px<br /><applet load="2o02" size="350" color="white" frame="true" align="right" spinBox="true" caption="2o02, resolution 1.500Å" /> '''Phosphorylation ind...) |
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==Overview== | ==Overview== | ||
| - | 14-3-3 proteins are phosphoserine/phosphothreonine-recognizing adapter | + | 14-3-3 proteins are phosphoserine/phosphothreonine-recognizing adapter proteins that regulate the activity of a vast array of targets. There are also examples of 14-3-3 proteins binding their targets via unphosphorylated motifs. Here we present a structural and biological investigation of the phosphorylation-independent interaction between 14-3-3 and exoenzyme S (ExoS), an ADP-ribosyltransferase toxin of Pseudomonas aeruginosa. ExoS binds to 14-3-3 in a novel binding mode mostly relying on hydrophobic contacts. The 1.5 A crystal structure is supported by cytotoxicity analysis, which reveals that substitution of the corresponding hydrophobic residues significantly weakens the ability of ExoS to modify the endogenous targets RAS/RAP1 and to induce cell death. Furthermore, mutation of key residues within the ExoS binding site for 14-3-3 impairs virulence in a mouse pneumonia model. In conclusion, we show that ExoS binds 14-3-3 in a novel reversed orientation that is primarily dependent on hydrophobic residues. This interaction is phosphorylation independent and is required for the function of ExoS. |
==About this Structure== | ==About this Structure== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Hallberg, B.]] | [[Category: Hallberg, B.]] | ||
| - | [[Category: Hauser, A | + | [[Category: Hauser, A R.]] |
[[Category: Ottmann, C.]] | [[Category: Ottmann, C.]] | ||
[[Category: Weyand, M.]] | [[Category: Weyand, M.]] | ||
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[[Category: protein binding/toxin complex]] | [[Category: protein binding/toxin complex]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:13:00 2008'' |
Revision as of 16:13, 21 February 2008
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Phosphorylation independent interactions between 14-3-3 and Exoenzyme S: from structure to pathogenesis
Overview
14-3-3 proteins are phosphoserine/phosphothreonine-recognizing adapter proteins that regulate the activity of a vast array of targets. There are also examples of 14-3-3 proteins binding their targets via unphosphorylated motifs. Here we present a structural and biological investigation of the phosphorylation-independent interaction between 14-3-3 and exoenzyme S (ExoS), an ADP-ribosyltransferase toxin of Pseudomonas aeruginosa. ExoS binds to 14-3-3 in a novel binding mode mostly relying on hydrophobic contacts. The 1.5 A crystal structure is supported by cytotoxicity analysis, which reveals that substitution of the corresponding hydrophobic residues significantly weakens the ability of ExoS to modify the endogenous targets RAS/RAP1 and to induce cell death. Furthermore, mutation of key residues within the ExoS binding site for 14-3-3 impairs virulence in a mouse pneumonia model. In conclusion, we show that ExoS binds 14-3-3 in a novel reversed orientation that is primarily dependent on hydrophobic residues. This interaction is phosphorylation independent and is required for the function of ExoS.
About this Structure
2O02 is a Single protein structure of sequence from Homo sapiens with as ligand. Full crystallographic information is available from OCA.
Reference
Phosphorylation-independent interaction between 14-3-3 and exoenzyme S: from structure to pathogenesis., Ottmann C, Yasmin L, Weyand M, Veesenmeyer JL, Diaz MH, Palmer RH, Francis MS, Hauser AR, Wittinghofer A, Hallberg B, EMBO J. 2007 Feb 7;26(3):902-13. Epub 2007 Jan 18. PMID:17235285
Page seeded by OCA on Thu Feb 21 18:13:00 2008
