2ez5: Difference between revisions

Revision as of 18:16, 21 February 2008

Solution Structure of the dNedd4 WW3* Domain- Comm LPSY Peptide Complex

OverviewOverview

Interactions between the WW domains of Drosophila Nedd4 (dNedd4) and Commissureless (Comm) PY motifs promote axon crossing at the CNS midline and muscle synaptogenesis. Here we report the solution structure of the dNedd4 WW3* domain complexed to the second PY motif (227'TGLPSYDEALH237') of Comm. Unexpectedly, there are interactions between WW3* and ligand residues both N- and C-terminal to the PY motif. Residues Y232'-L236' form a helical turn, following the PPII helical PY motif. Mutagenesis and binding studies confirm the importance of these extensive contacts, not simultaneously observed in other WW domain complexes, and identify a variable loop in WW3* responsible for its high-affinity interaction. These studies expand our general understanding of the molecular determinants involved in WW domain-ligand recognition. In addition, they provide insights into the specific regulation of dNedd4-mediated ubiquitination of Comm and subsequent internalization of Comm or the Comm/Roundabout complex, critical for CNS and muscle development.

About this StructureAbout this Structure

2EZ5 is a Protein complex structure of sequences from Drosophila melanogaster. Full crystallographic information is available from OCA.

ReferenceReference

Structural determinants for high-affinity binding in a Nedd4 WW3* domain-Comm PY motif complex., Kanelis V, Bruce MC, Skrynnikov NR, Rotin D, Forman-Kay JD, Structure. 2006 Mar;14(3):543-53. PMID:16531238

Page seeded by OCA on Thu Feb 21 17:16:02 2008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

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-[[Image:2ez5.gif|left|200px]]<br /><applet load="2ez5" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:2ez5.gif|left|200px]]<br /><applet load="2ez5" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="2ez5" />
 '''Solution Structure of the dNedd4 WW3* Domain- Comm LPSY Peptide Complex'''<br />
 ==Overview==
-Interactions between the WW domains of Drosophila Nedd4 (dNedd4) and, Commissureless (Comm) PY motifs promote axon crossing at the CNS midline, and muscle synaptogenesis. Here we report the solution structure of the, dNedd4 WW3* domain complexed to the second PY motif (227'TGLPSYDEALH237'), of Comm. Unexpectedly, there are interactions between WW3* and ligand, residues both N- and C-terminal to the PY motif. Residues Y232'-L236' form, a helical turn, following the PPII helical PY motif. Mutagenesis and, binding studies confirm the importance of these extensive contacts, not, simultaneously observed in other WW domain complexes, and identify a, variable loop in WW3* responsible for its high-affinity interaction. These, studies expand our general understanding of the molecular determinants, involved in WW domain-ligand recognition. In addition, they provide, insights into the specific regulation of dNedd4-mediated ubiquitination of, Comm and subsequent internalization of Comm or the Comm/Roundabout, complex, critical for CNS and muscle development.
+Interactions between the WW domains of Drosophila Nedd4 (dNedd4) and Commissureless (Comm) PY motifs promote axon crossing at the CNS midline and muscle synaptogenesis. Here we report the solution structure of the dNedd4 WW3* domain complexed to the second PY motif (227'TGLPSYDEALH237') of Comm. Unexpectedly, there are interactions between WW3* and ligand residues both N- and C-terminal to the PY motif. Residues Y232'-L236' form a helical turn, following the PPII helical PY motif. Mutagenesis and binding studies confirm the importance of these extensive contacts, not simultaneously observed in other WW domain complexes, and identify a variable loop in WW3* responsible for its high-affinity interaction. These studies expand our general understanding of the molecular determinants involved in WW domain-ligand recognition. In addition, they provide insights into the specific regulation of dNedd4-mediated ubiquitination of Comm and subsequent internalization of Comm or the Comm/Roundabout complex, critical for CNS and muscle development.
 ==About this Structure==
-EZ5 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Drosophila_melanogaster Drosophila melanogaster]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2EZ5 OCA].
+EZ5 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Drosophila_melanogaster Drosophila melanogaster]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2EZ5 OCA].
 ==Reference==
@@ Line 13: / Line 13: @@
 [[Category: Drosophila melanogaster]]
 [[Category: Protein complex]]
-[[Category: Bruce, M.C.]]
+[[Category: Bruce, M C.]]
-[[Category: Forman-Kay, J.D.]]
+[[Category: Forman-Kay, J D.]]
 [[Category: Kanelis, V.]]
 [[Category: Rotin, D.]]
-[[Category: Skrynnikov, N.R.]]
+[[Category: Skrynnikov, N R.]]
 [[Category: nedd4; ww domain; commissureless; py motif; binding affinity]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 10:14:35 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:16:02 2008''