2bap: Difference between revisions

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[[Image:2bap.gif|left|200px]]<br /><applet load="2bap" size="~~450~~" color="white" frame="true" align="right" spinBox="true"

[[Image:2bap.gif|left|200px]]<br /><applet load="2bap" size="350" color="white" frame="true" align="right" spinBox="true"

caption="2bap, resolution 3.300Å" />

'''Crystal structure of the N-terminal mDia1 Armadillo Repeat Region and Dimerisation Domain in complex with the mDia1 autoregulatory domain (DAD)'''<br />

==Overview==

Formins induce the nucleation and polymerisation of unbranched actin, filaments via the formin-homology domains 1 and 2. Diaphanous-related, formins (Drfs) are regulated by a RhoGTPase-binding domain situated in the, amino-terminal (N-terminal) region and a carboxy-terminal, Diaphanous-autoregulatory domain (DAD), whose interaction stabilises an, autoinhibited inactive conformation. Binding of active Rho releases DAD, and activates the catalytic activity of mDia. Here, we report on the, interaction of DAD with the regulatory N-terminus of mDia1 (mDia(N)) and, its release by Rho*GTP. We have defined the elements required for tight, binding and solved the three-dimensional structure of a complex between an, mDia(N) construct and DAD by X-ray crystallography. The core DAD region is, an alpha-helical peptide, which binds in the most highly conserved region, of mDia(N) using mainly hydrophobic interactions. The structure suggests a, two-step mechanism for release of autoinhibition whereby Rho*GTP, although, having a partially nonoverlapping binding site, displaces DAD by ionic, repulsion and steric clashes. We show that Rho*GTP accelerates the, dissociation of DAD from the mDia(N)*DAD complex.

Formins induce the nucleation and polymerisation of unbranched actin filaments via the formin-homology domains 1 and 2. Diaphanous-related formins (Drfs) are regulated by a RhoGTPase-binding domain situated in the amino-terminal (N-terminal) region and a carboxy-terminal Diaphanous-autoregulatory domain (DAD), whose interaction stabilises an autoinhibited inactive conformation. Binding of active Rho releases DAD and activates the catalytic activity of mDia. Here, we report on the interaction of DAD with the regulatory N-terminus of mDia1 (mDia(N)) and its release by Rho*GTP. We have defined the elements required for tight binding and solved the three-dimensional structure of a complex between an mDia(N) construct and DAD by X-ray crystallography. The core DAD region is an alpha-helical peptide, which binds in the most highly conserved region of mDia(N) using mainly hydrophobic interactions. The structure suggests a two-step mechanism for release of autoinhibition whereby Rho*GTP, although having a partially nonoverlapping binding site, displaces DAD by ionic repulsion and steric clashes. We show that Rho*GTP accelerates the dissociation of DAD from the mDia(N)*DAD complex.

==About this Structure==

2BAP is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://~~ispc~~.weizmann.ac.il/oca-bin/ocashort?id=2BAP OCA].

2BAP is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2BAP OCA].

==Reference==

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[[Category: armadillo repeats]]

''Page seeded by [http://~~ispc~~.weizmann.ac.il/oca OCA ] on ~~Wed Nov~~ 21 08:40:~~58 2007~~''

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:35:48 2008''

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@@ Line 1: / Line 1: @@
-[[Image:2bap.gif|left|200px]]<br /><applet load="2bap" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:2bap.gif|left|200px]]<br /><applet load="2bap" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="2bap, resolution 3.300&Aring;" />
 '''Crystal structure of the N-terminal mDia1 Armadillo Repeat Region and Dimerisation Domain in complex with the mDia1 autoregulatory domain (DAD)'''<br />
 ==Overview==
-Formins induce the nucleation and polymerisation of unbranched actin, filaments via the formin-homology domains 1 and 2. Diaphanous-related, formins (Drfs) are regulated by a RhoGTPase-binding domain situated in the, amino-terminal (N-terminal) region and a carboxy-terminal, Diaphanous-autoregulatory domain (DAD), whose interaction stabilises an, autoinhibited inactive conformation. Binding of active Rho releases DAD, and activates the catalytic activity of mDia. Here, we report on the, interaction of DAD with the regulatory N-terminus of mDia1 (mDia(N)) and, its release by Rho*GTP. We have defined the elements required for tight, binding and solved the three-dimensional structure of a complex between an, mDia(N) construct and DAD by X-ray crystallography. The core DAD region is, an alpha-helical peptide, which binds in the most highly conserved region, of mDia(N) using mainly hydrophobic interactions. The structure suggests a, two-step mechanism for release of autoinhibition whereby Rho*GTP, although, having a partially nonoverlapping binding site, displaces DAD by ionic, repulsion and steric clashes. We show that Rho*GTP accelerates the, dissociation of DAD from the mDia(N)*DAD complex.
+Formins induce the nucleation and polymerisation of unbranched actin filaments via the formin-homology domains 1 and 2. Diaphanous-related formins (Drfs) are regulated by a RhoGTPase-binding domain situated in the amino-terminal (N-terminal) region and a carboxy-terminal Diaphanous-autoregulatory domain (DAD), whose interaction stabilises an autoinhibited inactive conformation. Binding of active Rho releases DAD and activates the catalytic activity of mDia. Here, we report on the interaction of DAD with the regulatory N-terminus of mDia1 (mDia(N)) and its release by Rho*GTP. We have defined the elements required for tight binding and solved the three-dimensional structure of a complex between an mDia(N) construct and DAD by X-ray crystallography. The core DAD region is an alpha-helical peptide, which binds in the most highly conserved region of mDia(N) using mainly hydrophobic interactions. The structure suggests a two-step mechanism for release of autoinhibition whereby Rho*GTP, although having a partially nonoverlapping binding site, displaces DAD by ionic repulsion and steric clashes. We show that Rho*GTP accelerates the dissociation of DAD from the mDia(N)*DAD complex.
 ==About this Structure==
-BAP is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2BAP OCA].
+BAP is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2BAP OCA].
 ==Reference==
@@ Line 20: / Line 20: @@
 [[Category: armadillo repeats]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 08:40:58 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:35:48 2008''