5hzv

From Proteopedia

(Difference between revisions)

Current revision

Crystal structure of the zona pellucida module of human endoglin/CD105

Structural highlights

5hzv is a 1 chain structure with sequence from Escherichia coli K-12 and Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.7Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

EGLN_HUMAN Heritable pulmonary arterial hypertension;Familial cerebral saccular aneurysm;Generalized juvenile polyposis/juvenile polyposis coli;Hereditary hemorrhagic telangiectasia. The disease is caused by variants affecting the gene represented in this entry.

Function

EGLN_HUMAN Vascular endothelium glycoprotein that plays an important role in the regulation of angiogenesis (PubMed:21737454, PubMed:23300529). Required for normal structure and integrity of adult vasculature (PubMed:7894484). Regulates the migration of vascular endothelial cells (PubMed:17540773). Required for normal extraembryonic angiogenesis and for embryonic heart development (By similarity). May regulate endothelial cell shape changes in response to blood flow, which drive vascular remodeling and establishment of normal vascular morphology during angiogenesis (By similarity). May play a critical role in the binding of endothelial cells to integrins and/or other RGD receptors (PubMed:1692830). Acts as a TGF-beta coreceptor and is involved in the TGF-beta/BMP signaling cascade that ultimately leads to the activation of SMAD transcription factors (PubMed:21737454, PubMed:22347366, PubMed:23300529, PubMed:8370410). Required for GDF2/BMP9 signaling through SMAD1 in endothelial cells and modulates TGFB1 signaling through SMAD3 (PubMed:21737454, PubMed:22347366, PubMed:23300529).[UniProtKB:Q63961]^[1] ^[2] ^[3] ^[4] ^[5] ^[6] MALE_ECOLI Involved in the high-affinity maltose membrane transport system MalEFGK. Initial receptor for the active transport of and chemotaxis toward maltooligosaccharides.

Publication Abstract from PubMed

Endoglin (ENG)/CD105 is an essential endothelial cell co-receptor of the transforming growth factor beta (TGF-beta) superfamily, mutated in hereditary hemorrhagic telangiectasia type 1 (HHT1) and involved in tumor angiogenesis and preeclampsia. Here, we present crystal structures of the ectodomain of human ENG and its complex with the ligand bone morphogenetic protein 9 (BMP9). BMP9 interacts with a hydrophobic surface of the N-terminal orphan domain of ENG, which adopts a new duplicated fold generated by circular permutation. The interface involves residues mutated in HHT1 and overlaps with the epitope of tumor-suppressing anti-ENG monoclonal TRC105. The structure of the C-terminal zona pellucida module suggests how two copies of ENG embrace homodimeric BMP9, whose binding is compatible with ligand recognition by type I but not type II receptors. These findings shed light on the molecular basis of the BMP signaling cascade, with implications for future therapeutic interventions in this fundamental pathway.

Structural Basis of the Human Endoglin-BMP9 Interaction: Insights into BMP Signaling and HHT1.,Saito T, Bokhove M, Croci R, Zamora-Caballero S, Han L, Letarte M, de Sanctis D, Jovine L Cell Rep. 2017 May 30;19(9):1917-1928. doi: 10.1016/j.celrep.2017.05.011. PMID:28564608^[7]

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

References

↑ Lee NY, Blobe GC. The interaction of endoglin with beta-arrestin2 regulates transforming growth factor-beta-mediated ERK activation and migration in endothelial cells. J Biol Chem. 2007 Jul 20;282(29):21507-17. PMID:17540773 doi:10.1074/jbc.M700176200
↑ Castonguay R, Werner ED, Matthews RG, Presman E, Mulivor AW, Solban N, Sako D, Pearsall RS, Underwood KW, Seehra J, Kumar R, Grinberg AV. Soluble endoglin specifically binds bone morphogenetic proteins 9 and 10 via its orphan domain, inhibits blood vessel formation, and suppresses tumor growth. J Biol Chem. 2011 Aug 26;286(34):30034-46. PMID:21737454 doi:10.1074/jbc.M111.260133
↑ Nolan-Stevaux O, Zhong W, Culp S, Shaffer K, Hoover J, Wickramasinghe D, Ruefli-Brasse A. Endoglin requirement for BMP9 signaling in endothelial cells reveals new mechanism of action for selective anti-endoglin antibodies. PLoS One. 2012;7(12):e50920. doi: 10.1371/journal.pone.0050920. Epub 2012 Dec 27. PMID:23300529 doi:http://dx.doi.org/10.1371/journal.pone.0050920
↑ McAllister KA, Grogg KM, Johnson DW, Gallione CJ, Baldwin MA, Jackson CE, Helmbold EA, Markel DS, McKinnon WC, Murrell J, et al.. Endoglin, a TGF-beta binding protein of endothelial cells, is the gene for hereditary haemorrhagic telangiectasia type 1. Nat Genet. 1994 Dec;8(4):345-51. PMID:7894484 doi:10.1038/ng1294-345
↑ Bellón T, Corbí A, Lastres P, Calés C, Cebrián M, Vera S, Cheifetz S, Massague J, Letarte M, Bernabéu C. Identification and expression of two forms of the human transforming growth factor-beta-binding protein endoglin with distinct cytoplasmic regions. Eur J Immunol. 1993 Sep;23(9):2340-5. PMID:8370410 doi:10.1002/eji.1830230943
↑ Gougos A, Letarte M. Primary structure of endoglin, an RGD-containing glycoprotein of human endothelial cells. J Biol Chem. 1990 May 25;265(15):8361-4 PMID:1692830
↑ Saito T, Bokhove M, Croci R, Zamora-Caballero S, Han L, Letarte M, de Sanctis D, Jovine L. Structural Basis of the Human Endoglin-BMP9 Interaction: Insights into BMP Signaling and HHT1. Cell Rep. 2017 May 30;19(9):1917-1928. doi: 10.1016/j.celrep.2017.05.011. PMID:28564608 doi:http://dx.doi.org/10.1016/j.celrep.2017.05.011

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5hzv"

@@ Line 1: / Line 1: @@
 ==Crystal structure of the zona pellucida module of human endoglin/CD105==
-<StructureSection load='5hzv' size='340' side='right' caption='[[5hzv]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
+<StructureSection load='5hzv' size='340' side='right'caption='[[5hzv]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5hzv]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5HZV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5HZV FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5hzv]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_K-12 Escherichia coli K-12] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5HZV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5HZV FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MAL:MALTOSE'>MAL</scene></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]] 2.7&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3d4g|3d4g]], [[3nk4|3nk4]], [[4wrn|4wrn]], [[5i04|5i04]], [[5hzw|5hzw]], [[5i05|5i05]]</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GLC:ALPHA-D-GLUCOSE'>GLC</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PRD_900001:alpha-maltose'>PRD_900001</scene></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5hzv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5hzv OCA], [http://pdbe.org/5hzv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5hzv RCSB], [http://www.ebi.ac.uk/pdbsum/5hzv PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5hzv ProSAT]</span></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=5hzv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5hzv OCA], [https://pdbe.org/5hzv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5hzv RCSB], [https://www.ebi.ac.uk/pdbsum/5hzv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5hzv ProSAT]</span></td></tr>
 </table>
+== Disease ==
+[https://www.uniprot.org/uniprot/EGLN_HUMAN EGLN_HUMAN] Heritable pulmonary arterial hypertension;Familial cerebral saccular aneurysm;Generalized juvenile polyposis/juvenile polyposis coli;Hereditary hemorrhagic telangiectasia. The disease is caused by variants affecting the gene represented in this entry.
 == Function ==
-[[http://www.uniprot.org/uniprot/MALE_ECOLI MALE_ECOLI]] Involved in the high-affinity maltose membrane transport system MalEFGK. Initial receptor for the active transport of and chemotaxis toward maltooligosaccharides.
+[https://www.uniprot.org/uniprot/EGLN_HUMAN EGLN_HUMAN] Vascular endothelium glycoprotein that plays an important role in the regulation of angiogenesis (PubMed:21737454, PubMed:23300529). Required for normal structure and integrity of adult vasculature (PubMed:7894484). Regulates the migration of vascular endothelial cells (PubMed:17540773). Required for normal extraembryonic angiogenesis and for embryonic heart development (By similarity). May regulate endothelial cell shape changes in response to blood flow, which drive vascular remodeling and establishment of normal vascular morphology during angiogenesis (By similarity). May play a critical role in the binding of endothelial cells to integrins and/or other RGD receptors (PubMed:1692830). Acts as a TGF-beta coreceptor and is involved in the TGF-beta/BMP signaling cascade that ultimately leads to the activation of SMAD transcription factors (PubMed:21737454, PubMed:22347366, PubMed:23300529, PubMed:8370410). Required for GDF2/BMP9 signaling through SMAD1 in endothelial cells and modulates TGFB1 signaling through SMAD3 (PubMed:21737454, PubMed:22347366, PubMed:23300529).[UniProtKB:Q63961]<ref>PMID:17540773</ref> <ref>PMID:21737454</ref> <ref>PMID:23300529</ref> <ref>PMID:7894484</ref> <ref>PMID:8370410</ref> <ref>PMID:1692830</ref> [https://www.uniprot.org/uniprot/MALE_ECOLI MALE_ECOLI] Involved in the high-affinity maltose membrane transport system MalEFGK. Initial receptor for the active transport of and chemotaxis toward maltooligosaccharides.
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 23: / Line 25: @@
 __TOC__
 </StructureSection>
-[[Category: Bokhove, M]]
+[[Category: Escherichia coli K-12]]
-[[Category: Jovine, L]]
+[[Category: Homo sapiens]]
-[[Category: Saito, T]]
+[[Category: Large Structures]]
-[[Category: Angiogenesis]]
+[[Category: Bokhove M]]
-[[Category: Glycoprotein]]
+[[Category: Jovine L]]
-[[Category: Receptor]]
+[[Category: Saito T]]
-[[Category: Signaling protein]]
-[[Category: Zona pellucida domain]]

5hzv

From Proteopedia

Current revision

Crystal structure of the zona pellucida module of human endoglin/CD105

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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