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[[Image:1b6c.gif|left|200px]]


{{Structure
==CRYSTAL STRUCTURE OF THE CYTOPLASMIC DOMAIN OF THE TYPE I TGF-BETA RECEPTOR IN COMPLEX WITH FKBP12==
|PDB= 1b6c |SIZE=350|CAPTION= <scene name='initialview01'>1b6c</scene>, resolution 2.6&Aring;
<StructureSection load='1b6c' size='340' side='right'caption='[[1b6c]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
|SITE=  
== Structural highlights ==
|LIGAND= <scene name='pdbligand=SO4:SULFATE ION'>SO4</scene>
<table><tr><td colspan='2'>[[1b6c]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1B6C OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1B6C FirstGlance]. <br>
|ACTIVITY= [http://en.wikipedia.org/wiki/Peptidylprolyl_isomerase Peptidylprolyl isomerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.2.1.8 5.2.1.8]  
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.6&#8491;</td></tr>
|GENE=  
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
}}
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1b6c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1b6c OCA], [https://pdbe.org/1b6c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1b6c RCSB], [https://www.ebi.ac.uk/pdbsum/1b6c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1b6c ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/FKB1A_HUMAN FKB1A_HUMAN] Keeps in an inactive conformation TGFBR1, the TGF-beta type I serine/threonine kinase receptor, preventing TGF-beta receptor activation in absence of ligand. Recruites SMAD7 to ACVR1B which prevents the association of SMAD2 and SMAD3 with the activin receptor complex, thereby blocking the activin signal. May modulate the RYR1 calcium channel activity. PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides.<ref>PMID:9233797</ref> <ref>PMID:16720724</ref>
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/b6/1b6c_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1b6c ConSurf].
<div style="clear:both"></div>


'''CRYSTAL STRUCTURE OF THE CYTOPLASMIC DOMAIN OF THE TYPE I TGF-BETA RECEPTOR IN COMPLEX WITH FKBP12'''
==See Also==
 
*[[FKBP 3D structures|FKBP 3D structures]]
 
*[[TGF-beta receptor 3D structures|TGF-beta receptor 3D structures]]
==Overview==
== References ==
Activation of the type I TGFbeta receptor (TbetaR-I) requires phosphorylation of a regulatory segment known as the GS region, located upstream of the serine/threonine kinase domain in the cytoplasmic portion of the receptor. The crystal structure of a fragment of unphosphorylated TbetaR-I, containing both the GS region and the catalytic domain, has been determined in complex with the FK506-binding protein FKBP12. TbetaR-I adopts an inactive conformation that is maintained by the unphosphorylated GS region. FKBP12 binds to the GS region of the receptor, capping the TbetaR-II phosphorylation sites and further stabilizing the inactive conformation of TbetaR-I. Certain structural features at the catalytic center of TbetaR-I are characteristic of tyrosine kinases rather than Ser/Thr kinases.
<references/>
 
__TOC__
==Disease==
</StructureSection>
Known diseases associated with this structure: Loeys-Dietz syndrome, type 1A OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=190181 190181]], Loeys-Dietz syndrome, type 2A OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=190181 190181]]
 
==About this Structure==
1B6C is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1B6C OCA].
 
==Reference==
Crystal structure of the cytoplasmic domain of the type I TGF beta receptor in complex with FKBP12., Huse M, Chen YG, Massague J, Kuriyan J, Cell. 1999 Feb 5;96(3):425-36. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/10025408 10025408]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Peptidylprolyl isomerase]]
[[Category: Large Structures]]
[[Category: Protein complex]]
[[Category: Chen Y-G]]
[[Category: Chen, Y G.]]
[[Category: Huse M]]
[[Category: Huse, M.]]
[[Category: Kuriyan J]]
[[Category: Kuriyan, J.]]
[[Category: Massague J]]
[[Category: Massague, J.]]
[[Category: SO4]]
[[Category: complex (isomerase/protein kinase)]]
[[Category: receptor serine/threonine kinase]]
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 10:06:51 2008''

Latest revision as of 09:34, 7 February 2024

CRYSTAL STRUCTURE OF THE CYTOPLASMIC DOMAIN OF THE TYPE I TGF-BETA RECEPTOR IN COMPLEX WITH FKBP12CRYSTAL STRUCTURE OF THE CYTOPLASMIC DOMAIN OF THE TYPE I TGF-BETA RECEPTOR IN COMPLEX WITH FKBP12

Structural highlights

1b6c is a 8 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.6Å
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

FKB1A_HUMAN Keeps in an inactive conformation TGFBR1, the TGF-beta type I serine/threonine kinase receptor, preventing TGF-beta receptor activation in absence of ligand. Recruites SMAD7 to ACVR1B which prevents the association of SMAD2 and SMAD3 with the activin receptor complex, thereby blocking the activin signal. May modulate the RYR1 calcium channel activity. PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides.[1] [2]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

See Also

References

  1. ↑ Chen YG, Liu F, Massague J. Mechanism of TGFbeta receptor inhibition by FKBP12. EMBO J. 1997 Jul 1;16(13):3866-76. PMID:9233797 doi:10.1093/emboj/16.13.3866
  2. ↑ Yamaguchi T, Kurisaki A, Yamakawa N, Minakuchi K, Sugino H. FKBP12 functions as an adaptor of the Smad7-Smurf1 complex on activin type I receptor. J Mol Endocrinol. 2006 Jun;36(3):569-79. PMID:16720724 doi:10.1677/jme.1.01966

1b6c, resolution 2.60Å

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