1ias
From Proteopedia
(New page: 200px<br /> <applet load="1ias" size="450" color="white" frame="true" align="right" spinBox="true" caption="1ias, resolution 2.9Å" /> '''CYTOPLASMIC DOMAIN O...) |
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| - | [[Image:1ias.gif|left|200px]]<br /> | + | [[Image:1ias.gif|left|200px]]<br /><applet load="1ias" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1ias" size=" | + | |
caption="1ias, resolution 2.9Å" /> | caption="1ias, resolution 2.9Å" /> | ||
'''CYTOPLASMIC DOMAIN OF UNPHOSPHORYLATED TYPE I TGF-BETA RECEPTOR CRYSTALLIZED WITHOUT FKBP12'''<br /> | '''CYTOPLASMIC DOMAIN OF UNPHOSPHORYLATED TYPE I TGF-BETA RECEPTOR CRYSTALLIZED WITHOUT FKBP12'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The type I TGF beta receptor (T beta R-I) is activated by phosphorylation | + | The type I TGF beta receptor (T beta R-I) is activated by phosphorylation of the GS region, a conserved juxtamembrane segment located just N-terminal to the kinase domain. We have studied the molecular mechanism of receptor activation using a homogeneously tetraphosphorylated form of T beta R-I, prepared using protein semisynthesis. Phosphorylation of the GS region dramatically enhances the specificity of T beta R-I for the critical C-terminal serines of Smad2. In addition, tetraphosphorylated T beta R-I is bound specifically by Smad2 in a phosphorylation-dependent manner and is no longer recognized by the inhibitory protein FKBP12. Thus, phosphorylation activates T beta R-I by switching the GS region from a binding site for an inhibitor into a binding surface for substrate. Our observations suggest that phosphoserine/phosphothreonine-dependent localization is a key feature of the T beta R-I/Smad activation process. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1IAS 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 SO4 as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] Full crystallographic information is available from [http:// | + | 1IAS 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=SO4:'>SO4</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1IAS OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Non-specific serine/threonine protein kinase]] | [[Category: Non-specific serine/threonine protein kinase]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Chen, Y | + | [[Category: Chen, Y G.]] |
[[Category: Huse, M.]] | [[Category: Huse, M.]] | ||
[[Category: Kuriyan, J.]] | [[Category: Kuriyan, J.]] | ||
[[Category: Massague, J.]] | [[Category: Massague, J.]] | ||
| - | [[Category: Muir, T | + | [[Category: Muir, T W.]] |
[[Category: SO4]] | [[Category: SO4]] | ||
[[Category: gs region]] | [[Category: gs region]] | ||
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[[Category: tgf-beta receptor]] | [[Category: tgf-beta receptor]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:09:51 2008'' |
Revision as of 11:09, 21 February 2008
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CYTOPLASMIC DOMAIN OF UNPHOSPHORYLATED TYPE I TGF-BETA RECEPTOR CRYSTALLIZED WITHOUT FKBP12
Contents |
Overview
The type I TGF beta receptor (T beta R-I) is activated by phosphorylation of the GS region, a conserved juxtamembrane segment located just N-terminal to the kinase domain. We have studied the molecular mechanism of receptor activation using a homogeneously tetraphosphorylated form of T beta R-I, prepared using protein semisynthesis. Phosphorylation of the GS region dramatically enhances the specificity of T beta R-I for the critical C-terminal serines of Smad2. In addition, tetraphosphorylated T beta R-I is bound specifically by Smad2 in a phosphorylation-dependent manner and is no longer recognized by the inhibitory protein FKBP12. Thus, phosphorylation activates T beta R-I by switching the GS region from a binding site for an inhibitor into a binding surface for substrate. Our observations suggest that phosphoserine/phosphothreonine-dependent localization is a key feature of the T beta R-I/Smad activation process.
Disease
Known diseases associated with this structure: Aortic aneurysm, familial thoracic 5 OMIM:[190181], Furlong syndrome OMIM:[190181], Loeys-Dietz syndrome OMIM:[190181]
About this Structure
1IAS is a Single protein structure of sequence from Homo sapiens with as ligand. Active as Non-specific serine/threonine protein kinase, with EC number 2.7.11.1 Full crystallographic information is available from OCA.
Reference
The TGF beta receptor activation process: an inhibitor- to substrate-binding switch., Huse M, Muir TW, Xu L, Chen YG, Kuriyan J, Massague J, Mol Cell. 2001 Sep;8(3):671-82. PMID:11583628
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