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2pjy

From Proteopedia

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Structural basis for cooperative assembly of the TGF-beta signaling complex

Structural highlights

2pjy is a 3 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 3Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

TGFB3_HUMAN Defects in TGFB3 are a cause of familial arrhythmogenic right ventricular dysplasia type 1 (ARVD1) [MIM:107970; also known as arrhythmogenic right ventricular cardiomyopathy 1 (ARVC1). ARVD is an autosomal dominant disease characterized by partial degeneration of the myocardium of the right ventricle, electrical instability, and sudden death. It is clinically defined by electrocardiographic and angiographic criteria; pathologic findings, replacement of ventricular myocardium with fatty and fibrous elements, preferentially involve the right ventricular free wall.^[1]

Function

TGFB3_HUMAN Involved in embryogenesis and cell differentiation.

Evolutionary Conservation

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

Publication Abstract from PubMed

Dimeric ligands of the transforming growth factor-beta (TGF-beta) superfamily signal across cell membranes in a distinctive manner by assembling heterotetrameric complexes of structurally related serine/threonine-kinase receptor pairs. Unlike complexes of the bone morphogenetic protein (BMP) branch that apparently form due to avidity from membrane localization, TGF-beta complexes assemble cooperatively through recruitment of the low-affinity (type I) receptor by the ligand-bound high-affinity (type II) pair. Here we report the crystal structure of TGF-beta3 in complex with the extracellular domains of both pairs of receptors, revealing that the type I docks and becomes tethered via unique extensions at a composite ligand-type II interface. Disrupting the receptor-receptor interactions conferred by these extensions abolishes assembly of the signaling complex and signal transduction (Smad activation). Although structurally similar, BMP and TGF-beta receptors bind in dramatically different modes, mediating graded and switch-like assembly mechanisms that may have coevolved with branch-specific groups of cytoplasmic effectors.

Cooperative assembly of TGF-beta superfamily signaling complexes is mediated by two disparate mechanisms and distinct modes of receptor binding.,Groppe J, Hinck CS, Samavarchi-Tehrani P, Zubieta C, Schuermann JP, Taylor AB, Schwarz PM, Wrana JL, Hinck AP Mol Cell. 2008 Feb 1;29(2):157-68. PMID:18243111^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Beffagna G, Occhi G, Nava A, Vitiello L, Ditadi A, Basso C, Bauce B, Carraro G, Thiene G, Towbin JA, Danieli GA, Rampazzo A. Regulatory mutations in transforming growth factor-beta3 gene cause arrhythmogenic right ventricular cardiomyopathy type 1. Cardiovasc Res. 2005 Feb 1;65(2):366-73. PMID:15639475 doi:S0008-6363(04)00440-7
↑ Groppe J, Hinck CS, Samavarchi-Tehrani P, Zubieta C, Schuermann JP, Taylor AB, Schwarz PM, Wrana JL, Hinck AP. Cooperative assembly of TGF-beta superfamily signaling complexes is mediated by two disparate mechanisms and distinct modes of receptor binding. Mol Cell. 2008 Feb 1;29(2):157-68. PMID:18243111 doi:10.1016/j.molcel.2007.11.039

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 See Also
7 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2pjy"

Categories: Homo sapiens | Large Structures | Groppe J | Zubieta C

@@ Line 4: / Line 4: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[2pjy]] is a 3 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=2PJY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2PJY FirstGlance]. <br>
-</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=2pjy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2pjy OCA], [https://pdbe.org/2pjy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2pjy RCSB], [https://www.ebi.ac.uk/pdbsum/2pjy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2pjy ProSAT]</span></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3&#8491;</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=2pjy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2pjy OCA], [https://pdbe.org/2pjy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2pjy RCSB], [https://www.ebi.ac.uk/pdbsum/2pjy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2pjy ProSAT]</span></td></tr>
 </table>
 == Disease ==

2pjy

From Proteopedia

Current revision

Structural basis for cooperative assembly of the TGF-beta signaling complex

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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