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1khu

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Revision as of 09:33, 6 November 2019

Smad1 crystal structure reveals the details of BMP signaling pathway

Structural highlights

1khu is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[SMAD1_HUMAN] Defects in SMAD1 may be a cause of primary pulmonary hypertension (PPH1) [MIM:178600]. A rare disorder characterized by plexiform lesions of proliferating endothelial cells in pulmonary arterioles. The lesions lead to elevated pulmonary arterial pression, right ventricular failure, and death. The disease can occur from infancy throughout life and it has a mean age at onset of 36 years. Penetrance is reduced. Although familial PPH1 is rare, cases secondary to known etiologies are more common and include those associated with the appetite-suppressant drugs.^[1]

Function

[SMAD1_HUMAN] Transcriptional modulator activated by BMP (bone morphogenetic proteins) type 1 receptor kinase. SMAD1 is a receptor-regulated SMAD (R-SMAD). SMAD1/OAZ1/PSMB4 complex mediates the degradation of the CREBBP/EP300 repressor SNIP1.^[2]

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

Phosphorylation of Smad1 at the conserved carboxyl terminal SVS sequence activates BMP signaling. Here we report the crystal structure of the Smad1 MH2 domain in a conformation that reveals the structural effects of phosphorylation and a molecular mechanism for activation. Within a trimeric subunit assembly, the SVS sequence docks near two putative phosphoserine binding pockets of the neighboring molecule, in a position ready to interact upon phosphorylation. The MH2 domain undergoes concerted conformational changes upon activation, which signal Smad1 dissociation from the receptor kinase for subsequent heteromeric assembly with Smad4. Biochemical and modeling studies reveal unique favorable interactions within the Smad1/Smad4 heteromeric interface, providing a structural basis for their association in signaling.

Structural basis of Smad1 activation by receptor kinase phosphorylation.,Qin BY, Chacko BM, Lam SS, de Caestecker MP, Correia JJ, Lin K Mol Cell. 2001 Dec;8(6):1303-12. PMID:11779505^[3]

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

References

↑ Nasim MT, Ogo T, Ahmed M, Randall R, Chowdhury HM, Snape KM, Bradshaw TY, Southgate L, Lee GJ, Jackson I, Lord GM, Gibbs JS, Wilkins MR, Ohta-Ogo K, Nakamura K, Girerd B, Coulet F, Soubrier F, Humbert M, Morrell NW, Trembath RC, Machado RD. Molecular genetic characterization of SMAD signaling molecules in pulmonary arterial hypertension. Hum Mutat. 2011 Dec;32(12):1385-9. doi: 10.1002/humu.21605. Epub 2011 Oct 11. PMID:21898662 doi:10.1002/humu.21605
↑ Lin Y, Martin J, Gruendler C, Farley J, Meng X, Li BY, Lechleider R, Huff C, Kim RH, Grasser WA, Paralkar V, Wang T. A novel link between the proteasome pathway and the signal transduction pathway of the bone morphogenetic proteins (BMPs). BMC Cell Biol. 2002 Jun 21;3:15. PMID:12097147
↑ Qin BY, Chacko BM, Lam SS, de Caestecker MP, Correia JJ, Lin K. Structural basis of Smad1 activation by receptor kinase phosphorylation. Mol Cell. 2001 Dec;8(6):1303-12. PMID:11779505

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1khu"

@@ Line 1: / Line 1: @@
 ==Smad1 crystal structure reveals the details of BMP signaling pathway==
-<StructureSection load='1khu' size='340' side='right' caption='[[1khu]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
+<StructureSection load='1khu' size='340' side='right'caption='[[1khu]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
 == Structural highlights ==
 <table><tr><td colspan='2'>[[1khu]] is a 4 chain structure with sequence 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=1KHU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1KHU FirstGlance]. <br>
@@ Line 34: / Line 34: @@
 </StructureSection>
 [[Category: Homo sapiens]]
+[[Category: Large Structures]]
 [[Category: Lin, K]]
 [[Category: Qin, B Y]]
 [[Category: Beta-strand sandwich]]
 [[Category: Transcription]]

1khu

From Proteopedia

Revision as of 09:33, 6 November 2019

Smad1 crystal structure reveals the details of BMP signaling pathway

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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