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2joc

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(New page: 200px<br /><applet load="2joc" size="350" color="white" frame="true" align="right" spinBox="true" caption="2joc" /> '''Mouse Itch 3rd domain phosphorylated in T30'...)
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==Overview==
==Overview==
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In this work, we study the role of phosphorylation as a regulatory, mechanism for the interaction between the E3 ubiquitin ligase ItchWW3, domain and two PPxY motifs of one of its targets, the Epstein-Barr virus, latent membrane protein 2A. Whereas ligand phosphorylation only diminishes, binding, domain phosphorylation at residue T30 abrogates it. We show that, two ItchWW domains can be phosphorylated at this position, using CK2 and, PKA kinases and/or with stimulated T lymphocyte lysates. To better, understand the regulation process, we determined the NMR structures of the, ItchWW3-PPxY complex and of the phosphoT30-ItchWW3 variant. The peptide, binds the domain using both XP and tyrosine grooves. A hydrogen bond from, T30 to the ligand is also detected. This hydrogen-bond formation is, precluded in the variant, explaining the inhibition upon phosphorylation., Our results suggest that phosphorylation at position 30 in ItchWW domains, can be a mechanism to inhibit target recognition in vivo.
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In this work, we study the role of phosphorylation as a regulatory mechanism for the interaction between the E3 ubiquitin ligase ItchWW3 domain and two PPxY motifs of one of its targets, the Epstein-Barr virus latent membrane protein 2A. Whereas ligand phosphorylation only diminishes binding, domain phosphorylation at residue T30 abrogates it. We show that two ItchWW domains can be phosphorylated at this position, using CK2 and PKA kinases and/or with stimulated T lymphocyte lysates. To better understand the regulation process, we determined the NMR structures of the ItchWW3-PPxY complex and of the phosphoT30-ItchWW3 variant. The peptide binds the domain using both XP and tyrosine grooves. A hydrogen bond from T30 to the ligand is also detected. This hydrogen-bond formation is precluded in the variant, explaining the inhibition upon phosphorylation. Our results suggest that phosphorylation at position 30 in ItchWW domains can be a mechanism to inhibit target recognition in vivo.
==About this Structure==
==About this Structure==
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NMR structural studies of the ItchWW3 domain reveal that phosphorylation at T30 inhibits the interaction with PPxY-containing ligands., Morales B, Ramirez-Espain X, Shaw AZ, Martin-Malpartida P, Yraola F, Sanchez-Tillo E, Farrera C, Celada A, Royo M, Macias MJ, Structure. 2007 Apr;15(4):473-83. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17437719 17437719]
NMR structural studies of the ItchWW3 domain reveal that phosphorylation at T30 inhibits the interaction with PPxY-containing ligands., Morales B, Ramirez-Espain X, Shaw AZ, Martin-Malpartida P, Yraola F, Sanchez-Tillo E, Farrera C, Celada A, Royo M, Macias MJ, Structure. 2007 Apr;15(4):473-83. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17437719 17437719]
[[Category: Single protein]]
[[Category: Single protein]]
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[[Category: Macias, M.J.]]
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[[Category: Macias, M J.]]
[[Category: Martin-Malpartida, P.]]
[[Category: Martin-Malpartida, P.]]
[[Category: Morales, B.]]
[[Category: Morales, B.]]
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[[Category: Royo, M.]]
[[Category: Royo, M.]]
[[Category: Ruiz, L.]]
[[Category: Ruiz, L.]]
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[[Category: Shaw, A.Z.]]
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[[Category: Shaw, A Z.]]
[[Category: Yraola, F.]]
[[Category: Yraola, F.]]
[[Category: itch]]
[[Category: itch]]
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[[Category: ww]]
[[Category: ww]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 15:19:04 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:04:33 2008''

Revision as of 16:04, 21 February 2008

Image:2joc.gif

2joc

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Mouse Itch 3rd domain phosphorylated in T30

Overview

In this work, we study the role of phosphorylation as a regulatory mechanism for the interaction between the E3 ubiquitin ligase ItchWW3 domain and two PPxY motifs of one of its targets, the Epstein-Barr virus latent membrane protein 2A. Whereas ligand phosphorylation only diminishes binding, domain phosphorylation at residue T30 abrogates it. We show that two ItchWW domains can be phosphorylated at this position, using CK2 and PKA kinases and/or with stimulated T lymphocyte lysates. To better understand the regulation process, we determined the NMR structures of the ItchWW3-PPxY complex and of the phosphoT30-ItchWW3 variant. The peptide binds the domain using both XP and tyrosine grooves. A hydrogen bond from T30 to the ligand is also detected. This hydrogen-bond formation is precluded in the variant, explaining the inhibition upon phosphorylation. Our results suggest that phosphorylation at position 30 in ItchWW domains can be a mechanism to inhibit target recognition in vivo.

About this Structure

2JOC is a Single protein structure of sequence from [1]. Full crystallographic information is available from OCA.

Reference

NMR structural studies of the ItchWW3 domain reveal that phosphorylation at T30 inhibits the interaction with PPxY-containing ligands., Morales B, Ramirez-Espain X, Shaw AZ, Martin-Malpartida P, Yraola F, Sanchez-Tillo E, Farrera C, Celada A, Royo M, Macias MJ, Structure. 2007 Apr;15(4):473-83. PMID:17437719

Page seeded by OCA on Thu Feb 21 18:04:33 2008

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