1zvd: Difference between revisions

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[[Image:1zvd.gif|left|200px]]<br />

[[Image:1zvd.gif|left|200px]]<br /><applet load="1zvd" size="350" color="white" frame="true" align="right" spinBox="true"

<applet load="1zvd" size="~~450~~" color="white" frame="true" align="right" spinBox="true"

caption="1zvd, resolution 2.10Å" />

'''Regulation of Smurf2 Ubiquitin Ligase Activity by Anchoring the E2 to the HECT domain'''<br />

==Overview==

The conjugation of ubiquitin to proteins involves a cascade of activating, (E1), conjugating (E2), and ubiquitin-ligating (E3) type enzymes that, commonly signal protein destruction. In TGFbeta signaling the inhibitory, protein Smad7 recruits Smurf2, an E3 of the C2-WW-HECT domain class, to, the TGFbeta receptor complex to facilitate receptor degradation. Here, we, demonstrate that the amino-terminal domain (NTD) of Smad7 stimulates Smurf, activity by recruiting the E2, UbcH7, to the HECT domain. A 2.1 A, resolution X-ray crystal structure of the Smurf2 HECT domain reveals that, it has a suboptimal E2 binding pocket that could be optimized by, mutagenesis to generate a HECT domain that functions independently of, Smad7 and potently inhibits TGFbeta signaling. Thus, E2 enzyme recognition, by an E3 HECT enzyme is not constitutively competent and provides a point, of control for regulating the ubiquitin ligase activity through the action, of auxiliary proteins.

The conjugation of ubiquitin to proteins involves a cascade of activating (E1), conjugating (E2), and ubiquitin-ligating (E3) type enzymes that commonly signal protein destruction. In TGFbeta signaling the inhibitory protein Smad7 recruits Smurf2, an E3 of the C2-WW-HECT domain class, to the TGFbeta receptor complex to facilitate receptor degradation. Here, we demonstrate that the amino-terminal domain (NTD) of Smad7 stimulates Smurf activity by recruiting the E2, UbcH7, to the HECT domain. A 2.1 A resolution X-ray crystal structure of the Smurf2 HECT domain reveals that it has a suboptimal E2 binding pocket that could be optimized by mutagenesis to generate a HECT domain that functions independently of Smad7 and potently inhibits TGFbeta signaling. Thus, E2 enzyme recognition by an E3 HECT enzyme is not constitutively competent and provides a point of control for regulating the ubiquitin ligase activity through the action of auxiliary proteins.

==About this Structure==

1ZVD is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with NA and PO4 as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://~~ispc~~.weizmann.ac.il/oca-bin/ocashort?id=1ZVD OCA].

1ZVD is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=NA:'>NA</scene> and <scene name='pdbligand=PO4:'>PO4</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ZVD OCA].

==Reference==

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[[Category: Homo sapiens]]

[[Category: Single protein]]

[[Category: Briant, D.J.]]

[[Category: Briant, D J.]]

[[Category: Guglielmo, G.M.Di.]]

[[Category: Guglielmo, G M.Di.]]

[[Category: Kavsak, P.]]

[[Category: Ogunjimi, A.A.]]

[[Category: Ogunjimi, A A.]]

[[Category: Pece-Barbara, N.]]

[[Category: Rasmussen, R.K.]]

[[Category: Rasmussen, R K.]]

[[Category: Roy, C.Le.]]

[[Category: Roy, C Le.]]

[[Category: Seet, B.T.]]

[[Category: Seet, B T.]]

[[Category: Sicheri, F.]]

[[Category: Wrana, J.L.]]

[[Category: Wrana, J L.]]

[[Category: NA]]

[[Category: PO4]]

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[[Category: x-ray crystal structure]]

''Page seeded by [http://~~ispc~~.weizmann.ac.il/oca OCA ] on ~~Mon Nov 12 20~~:41:~~50 2007~~''

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:19:26 2008''

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@@ Line 1: / Line 1: @@
-[[Image:1zvd.gif|left|200px]]<br />
+[[Image:1zvd.gif|left|200px]]<br /><applet load="1zvd" size="350" color="white" frame="true" align="right" spinBox="true"
-<applet load="1zvd" size="450" color="white" frame="true" align="right" spinBox="true"
 caption="1zvd, resolution 2.10&Aring;" />
 '''Regulation of Smurf2 Ubiquitin Ligase Activity by Anchoring the E2 to the HECT domain'''<br />
 ==Overview==
-The conjugation of ubiquitin to proteins involves a cascade of activating, (E1), conjugating (E2), and ubiquitin-ligating (E3) type enzymes that, commonly signal protein destruction. In TGFbeta signaling the inhibitory, protein Smad7 recruits Smurf2, an E3 of the C2-WW-HECT domain class, to, the TGFbeta receptor complex to facilitate receptor degradation. Here, we, demonstrate that the amino-terminal domain (NTD) of Smad7 stimulates Smurf, activity by recruiting the E2, UbcH7, to the HECT domain. A 2.1 A, resolution X-ray crystal structure of the Smurf2 HECT domain reveals that, it has a suboptimal E2 binding pocket that could be optimized by, mutagenesis to generate a HECT domain that functions independently of, Smad7 and potently inhibits TGFbeta signaling. Thus, E2 enzyme recognition, by an E3 HECT enzyme is not constitutively competent and provides a point, of control for regulating the ubiquitin ligase activity through the action, of auxiliary proteins.
+The conjugation of ubiquitin to proteins involves a cascade of activating (E1), conjugating (E2), and ubiquitin-ligating (E3) type enzymes that commonly signal protein destruction. In TGFbeta signaling the inhibitory protein Smad7 recruits Smurf2, an E3 of the C2-WW-HECT domain class, to the TGFbeta receptor complex to facilitate receptor degradation. Here, we demonstrate that the amino-terminal domain (NTD) of Smad7 stimulates Smurf activity by recruiting the E2, UbcH7, to the HECT domain. A 2.1 A resolution X-ray crystal structure of the Smurf2 HECT domain reveals that it has a suboptimal E2 binding pocket that could be optimized by mutagenesis to generate a HECT domain that functions independently of Smad7 and potently inhibits TGFbeta signaling. Thus, E2 enzyme recognition by an E3 HECT enzyme is not constitutively competent and provides a point of control for regulating the ubiquitin ligase activity through the action of auxiliary proteins.
 ==About this Structure==
-ZVD is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with NA and PO4 as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1ZVD OCA].
+ZVD is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=NA:'>NA</scene> and <scene name='pdbligand=PO4:'>PO4</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ZVD OCA].
 ==Reference==
@@ Line 14: / Line 13: @@
 [[Category: Homo sapiens]]
 [[Category: Single protein]]
-[[Category: Briant, D.J.]]
+[[Category: Briant, D J.]]
-[[Category: Guglielmo, G.M.Di.]]
+[[Category: Guglielmo, G M.Di.]]
 [[Category: Kavsak, P.]]
-[[Category: Ogunjimi, A.A.]]
+[[Category: Ogunjimi, A A.]]
 [[Category: Pece-Barbara, N.]]
-[[Category: Rasmussen, R.K.]]
+[[Category: Rasmussen, R K.]]
-[[Category: Roy, C.Le.]]
+[[Category: Roy, C Le.]]
-[[Category: Seet, B.T.]]
+[[Category: Seet, B T.]]
 [[Category: Sicheri, F.]]
-[[Category: Wrana, J.L.]]
+[[Category: Wrana, J L.]]
 [[Category: NA]]
 [[Category: PO4]]
@@ Line 30: / Line 29: @@
 [[Category: x-ray crystal structure]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 20:41:50 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:19:26 2008''