2hmh: Difference between revisions

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

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

caption="2hmh, resolution 2.00Å" />

'''Crystal structure of SOCS3 in complex with gp130(pTyr757) phosphopeptide.'''<br />

==Overview==

Suppressor of cytokine signaling (SOCS) proteins are indispensable, negative regulators of cytokine-stimulated Janus kinase (JAK)-signal, transducer and activator of transcription (STAT) signaling pathways. SOCS, proteins (SOCS1-7 and CIS) consist of a variable N-terminal region, a, central Src homology-2 (SH2) domain, and a C-terminal SOCS box. The, N-terminal region in SOCS1 and SOCS3 includes the so-called kinase, inhibitory region that has been shown to inhibit the catalytic activity of, JAK2. Here, we present a crystal structure at 2.0 A resolution of the, N-terminally extended SH2 domain of SOCS3 in complex with its, phosphopeptide target on the cytokine receptor gp130. The structure, reveals that major insertions in the EF and BG loops of the SOCS3 SH2, domain are responsible for binding to gp130 with high affinity and, specificity. In addition, the structure provides insights into the, possible mechanisms by which SOCS3 and SOCS1 inhibit JAK2 kinase activity.

Suppressor of cytokine signaling (SOCS) proteins are indispensable negative regulators of cytokine-stimulated Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathways. SOCS proteins (SOCS1-7 and CIS) consist of a variable N-terminal region, a central Src homology-2 (SH2) domain, and a C-terminal SOCS box. The N-terminal region in SOCS1 and SOCS3 includes the so-called kinase inhibitory region that has been shown to inhibit the catalytic activity of JAK2. Here, we present a crystal structure at 2.0 A resolution of the N-terminally extended SH2 domain of SOCS3 in complex with its phosphopeptide target on the cytokine receptor gp130. The structure reveals that major insertions in the EF and BG loops of the SOCS3 SH2 domain are responsible for binding to gp130 with high affinity and specificity. In addition, the structure provides insights into the possible mechanisms by which SOCS3 and SOCS1 inhibit JAK2 kinase activity.

==About this Structure==

2HMH 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=2HMH OCA].

2HMH 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=2HMH OCA].

==Reference==

Line 14:

[[Category: Protein complex]]

[[Category: Bergamin, E.]]

[[Category: Hubbard, S.R.]]

[[Category: Hubbard, S R.]]

[[Category: Wu, J.]]

[[Category: gp130]]

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[[Category: socs3]]

''Page seeded by [http://~~ispc~~.weizmann.ac.il/oca OCA ] on ~~Wed Nov~~ 21 11:50:~~45 2007~~''

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:43:28 2008''

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@@ Line 1: / Line 1: @@
-[[Image:2hmh.gif|left|200px]]<br /><applet load="2hmh" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:2hmh.gif|left|200px]]<br /><applet load="2hmh" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="2hmh, resolution 2.00&Aring;" />
 '''Crystal structure of SOCS3 in complex with gp130(pTyr757) phosphopeptide.'''<br />
 ==Overview==
-Suppressor of cytokine signaling (SOCS) proteins are indispensable, negative regulators of cytokine-stimulated Janus kinase (JAK)-signal, transducer and activator of transcription (STAT) signaling pathways. SOCS, proteins (SOCS1-7 and CIS) consist of a variable N-terminal region, a, central Src homology-2 (SH2) domain, and a C-terminal SOCS box. The, N-terminal region in SOCS1 and SOCS3 includes the so-called kinase, inhibitory region that has been shown to inhibit the catalytic activity of, JAK2. Here, we present a crystal structure at 2.0 A resolution of the, N-terminally extended SH2 domain of SOCS3 in complex with its, phosphopeptide target on the cytokine receptor gp130. The structure, reveals that major insertions in the EF and BG loops of the SOCS3 SH2, domain are responsible for binding to gp130 with high affinity and, specificity. In addition, the structure provides insights into the, possible mechanisms by which SOCS3 and SOCS1 inhibit JAK2 kinase activity.
+Suppressor of cytokine signaling (SOCS) proteins are indispensable negative regulators of cytokine-stimulated Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathways. SOCS proteins (SOCS1-7 and CIS) consist of a variable N-terminal region, a central Src homology-2 (SH2) domain, and a C-terminal SOCS box. The N-terminal region in SOCS1 and SOCS3 includes the so-called kinase inhibitory region that has been shown to inhibit the catalytic activity of JAK2. Here, we present a crystal structure at 2.0 A resolution of the N-terminally extended SH2 domain of SOCS3 in complex with its phosphopeptide target on the cytokine receptor gp130. The structure reveals that major insertions in the EF and BG loops of the SOCS3 SH2 domain are responsible for binding to gp130 with high affinity and specificity. In addition, the structure provides insights into the possible mechanisms by which SOCS3 and SOCS1 inhibit JAK2 kinase activity.
 ==About this Structure==
-HMH 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=2HMH OCA].
+HMH 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=2HMH OCA].
 ==Reference==
@@ Line 14: / Line 14: @@
 [[Category: Protein complex]]
 [[Category: Bergamin, E.]]
-[[Category: Hubbard, S.R.]]
+[[Category: Hubbard, S R.]]
 [[Category: Wu, J.]]
 [[Category: gp130]]
@@ Line 21: / Line 21: @@
 [[Category: socs3]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 11:50:45 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:43:28 2008''