1p5t: Difference between revisions

Line 1:

[[Image:1p5t.jpg|left|200px]]<br /><applet load="1p5t" size="~~450~~" color="white" frame="true" align="right" spinBox="true"

[[Image:1p5t.jpg|left|200px]]<br /><applet load="1p5t" size="350" color="white" frame="true" align="right" spinBox="true"

caption="1p5t, resolution 2.35Å" />

'''Crystal Structure of Dok1 PTB Domain'''<br />

==Overview==

Dok1 is a common substrate of activated protein-tyrosine kinases. It is, rapidly tyrosine-phosphorylated in response to receptor tyrosine, activation and interacts with ras GTPase-activating protein and Nck, leading to inhibition of ras signaling pathway activation and the c-Jun, N-terminal kinase (JNK) and c-Jun activation, respectively. In chronic, myelogenous leukemia cells, it has shown constitutive phosphorylation. The, N-terminal phosphotyrosine binding (PTB) domain of Dok1 can recognize and, bind specifically to phosphotyrosine-containing motifs of receptors. Here, we report the crystal structure of the Dok1 PTB domain alone and in, complex with a phosphopeptide derived from RET receptor tyrosine kinase., The structure consists of a beta-sandwich composed of two nearly, orthogonal, 7-stranded, antiparallel beta-sheets, and it is capped at one, side by a C-terminal alpha-helix. The RET phosphopeptide binds to Dok1 via, a surface groove formed between strand beta5 and the C-terminal, alpha-helix of the PTB domain. The structures reveal the molecular basis, for the specific recognition of RET by the Dok1 PTB domain. We also show, that Dok1 does not recognize peptide sequences from TrkA and IL-4, which, are recognized by Shc and IRS1, respectively.

Dok1 is a common substrate of activated protein-tyrosine kinases. It is rapidly tyrosine-phosphorylated in response to receptor tyrosine activation and interacts with ras GTPase-activating protein and Nck, leading to inhibition of ras signaling pathway activation and the c-Jun N-terminal kinase (JNK) and c-Jun activation, respectively. In chronic myelogenous leukemia cells, it has shown constitutive phosphorylation. The N-terminal phosphotyrosine binding (PTB) domain of Dok1 can recognize and bind specifically to phosphotyrosine-containing motifs of receptors. Here we report the crystal structure of the Dok1 PTB domain alone and in complex with a phosphopeptide derived from RET receptor tyrosine kinase. The structure consists of a beta-sandwich composed of two nearly orthogonal, 7-stranded, antiparallel beta-sheets, and it is capped at one side by a C-terminal alpha-helix. The RET phosphopeptide binds to Dok1 via a surface groove formed between strand beta5 and the C-terminal alpha-helix of the PTB domain. The structures reveal the molecular basis for the specific recognition of RET by the Dok1 PTB domain. We also show that Dok1 does not recognize peptide sequences from TrkA and IL-4, which are recognized by Shc and IRS1, respectively.

==About this Structure==

1P5T is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence 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=1P5T OCA].

1P5T is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence 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=1P5T OCA].

==Reference==

Line 24:

[[Category: signaling protein]]

''Page seeded by [http://~~ispc~~.weizmann.ac.il/oca OCA ] on ~~Tue Nov 20 23~~:29:~~49 2007~~''

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:25:25 2008''

Navigation menu

Page actions

Page actions

Personal tools

Navigation

Search

Tools

@@ Line 1: / Line 1: @@
-[[Image:1p5t.jpg|left|200px]]<br /><applet load="1p5t" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:1p5t.jpg|left|200px]]<br /><applet load="1p5t" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="1p5t, resolution 2.35&Aring;" />
 '''Crystal Structure of Dok1 PTB Domain'''<br />
 ==Overview==
-Dok1 is a common substrate of activated protein-tyrosine kinases. It is, rapidly tyrosine-phosphorylated in response to receptor tyrosine, activation and interacts with ras GTPase-activating protein and Nck, leading to inhibition of ras signaling pathway activation and the c-Jun, N-terminal kinase (JNK) and c-Jun activation, respectively. In chronic, myelogenous leukemia cells, it has shown constitutive phosphorylation. The, N-terminal phosphotyrosine binding (PTB) domain of Dok1 can recognize and, bind specifically to phosphotyrosine-containing motifs of receptors. Here, we report the crystal structure of the Dok1 PTB domain alone and in, complex with a phosphopeptide derived from RET receptor tyrosine kinase., The structure consists of a beta-sandwich composed of two nearly, orthogonal, 7-stranded, antiparallel beta-sheets, and it is capped at one, side by a C-terminal alpha-helix. The RET phosphopeptide binds to Dok1 via, a surface groove formed between strand beta5 and the C-terminal, alpha-helix of the PTB domain. The structures reveal the molecular basis, for the specific recognition of RET by the Dok1 PTB domain. We also show, that Dok1 does not recognize peptide sequences from TrkA and IL-4, which, are recognized by Shc and IRS1, respectively.
+Dok1 is a common substrate of activated protein-tyrosine kinases. It is rapidly tyrosine-phosphorylated in response to receptor tyrosine activation and interacts with ras GTPase-activating protein and Nck, leading to inhibition of ras signaling pathway activation and the c-Jun N-terminal kinase (JNK) and c-Jun activation, respectively. In chronic myelogenous leukemia cells, it has shown constitutive phosphorylation. The N-terminal phosphotyrosine binding (PTB) domain of Dok1 can recognize and bind specifically to phosphotyrosine-containing motifs of receptors. Here we report the crystal structure of the Dok1 PTB domain alone and in complex with a phosphopeptide derived from RET receptor tyrosine kinase. The structure consists of a beta-sandwich composed of two nearly orthogonal, 7-stranded, antiparallel beta-sheets, and it is capped at one side by a C-terminal alpha-helix. The RET phosphopeptide binds to Dok1 via a surface groove formed between strand beta5 and the C-terminal alpha-helix of the PTB domain. The structures reveal the molecular basis for the specific recognition of RET by the Dok1 PTB domain. We also show that Dok1 does not recognize peptide sequences from TrkA and IL-4, which are recognized by Shc and IRS1, respectively.
 ==About this Structure==
-P5T is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence 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=1P5T OCA].
+P5T is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence 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=1P5T OCA].
 ==Reference==
@@ Line 24: / Line 24: @@
 [[Category: signaling protein]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 23:29:49 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:25:25 2008''