2djy: Difference between revisions
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'''Solution structure of Smurf2 WW3 domain-Smad7 PY peptide complex'''<br /> | '''Solution structure of Smurf2 WW3 domain-Smad7 PY peptide complex'''<br /> | ||
==Overview== | ==Overview== | ||
Smurf2 is an E3 ubiquitin ligase that drives degradation of the | Smurf2 is an E3 ubiquitin ligase that drives degradation of the transforming growth factor-beta receptors and other targets. Recognition of the receptors by Smurf2 is accomplished through an intermediary protein, Smad7. Here we have demonstrated that the WW3 domain of Smurf2 can directly bind to the Smad7 polyproline-tyrosine (PY) motif. Of particular interest, the highly conserved WW domain binding site Trp, which interacts with target PY motifs, is a Phe in the Smurf2 WW3 domain. To examine this interaction, the solution structure of the complex between the Smad7 PY motif region (ELESPPPPYSRYPMD) and the Smurf2 WW3 domain was determined. The structure reveals that, in addition to binding the PY motif, the WW3 domain binds six residues C-terminal to the PY motif (PY-tail). Although the Phe in the WW3 domain binding site decreases affinity relative to the canonical Trp, this is balanced by additional interactions between the PY-tail and the beta1-strand and beta1-beta2 loop of the WW3 domain. The interaction between the Smurf2 WW3 domain and the Smad7 PY motif is the first example of PY motif recognition by a WW domain with a Phe substituted for the binding site Trp. This unusual interaction allows the Smurf2 WW3 domain to recognize a subset of PY motif-containing proteins utilizing an expanded surface to provide specificity. | ||
==Disease== | |||
Known diseases associated with this structure: Colorectal cancer, susceptiblity to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=602932 602932]] | |||
==About this Structure== | ==About this Structure== | ||
2DJY is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http:// | 2DJY is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2DJY OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Chong, P | [[Category: Chong, P A.]] | ||
[[Category: Forman-Kay, J | [[Category: Forman-Kay, J D.]] | ||
[[Category: Lin, H]] | [[Category: Lin, H]] | ||
[[Category: Wrana, J | [[Category: Wrana, J L.]] | ||
[[Category: beta sheet]] | [[Category: beta sheet]] | ||
[[Category: polyproline type ii helix]] | [[Category: polyproline type ii helix]] | ||
[[Category: ppii]] | [[Category: ppii]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:59:37 2008'' | ||
Revision as of 17:59, 21 February 2008
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Solution structure of Smurf2 WW3 domain-Smad7 PY peptide complex
OverviewOverview
Smurf2 is an E3 ubiquitin ligase that drives degradation of the transforming growth factor-beta receptors and other targets. Recognition of the receptors by Smurf2 is accomplished through an intermediary protein, Smad7. Here we have demonstrated that the WW3 domain of Smurf2 can directly bind to the Smad7 polyproline-tyrosine (PY) motif. Of particular interest, the highly conserved WW domain binding site Trp, which interacts with target PY motifs, is a Phe in the Smurf2 WW3 domain. To examine this interaction, the solution structure of the complex between the Smad7 PY motif region (ELESPPPPYSRYPMD) and the Smurf2 WW3 domain was determined. The structure reveals that, in addition to binding the PY motif, the WW3 domain binds six residues C-terminal to the PY motif (PY-tail). Although the Phe in the WW3 domain binding site decreases affinity relative to the canonical Trp, this is balanced by additional interactions between the PY-tail and the beta1-strand and beta1-beta2 loop of the WW3 domain. The interaction between the Smurf2 WW3 domain and the Smad7 PY motif is the first example of PY motif recognition by a WW domain with a Phe substituted for the binding site Trp. This unusual interaction allows the Smurf2 WW3 domain to recognize a subset of PY motif-containing proteins utilizing an expanded surface to provide specificity.
DiseaseDisease
Known diseases associated with this structure: Colorectal cancer, susceptiblity to OMIM:[602932]
About this StructureAbout this Structure
2DJY is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
An expanded WW domain recognition motif revealed by the interaction between Smad7 and the E3 ubiquitin ligase Smurf2., Chong PA, Lin H, Wrana JL, Forman-Kay JD, J Biol Chem. 2006 Jun 23;281(25):17069-75. Epub 2006 Apr 26. PMID:16641086
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