4gyx

From Proteopedia

(Difference between revisions)

Current revision

The von Willebrand Factor A3 domain binding region of type III collagen stabilized by the cysteine knot

Structural highlights

4gyx 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 1.49Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

CO3A1_HUMAN Defects in COL3A1 are a cause of Ehlers-Danlos syndrome type 3 (EDS3) [MIM:130020; also known as benign hypermobility syndrome. EDS is a connective tissue disorder characterized by hyperextensible skin, atrophic cutaneous scars due to tissue fragility and joint hyperlaxity. EDS3 is a form of Ehlers-Danlos syndrome characterized by marked joint hyperextensibility without skeletal deformity.^[1] Defects in COL3A1 are the cause of Ehlers-Danlos syndrome type 4 (EDS4) [MIM:130050. EDS is a connective tissue disorder characterized by hyperextensible skin, atrophic cutaneous scars due to tissue fragility and joint hyperlaxity. EDS4 is the most severe form of the disease. It is characterized by the joint and dermal manifestations as in other forms of the syndrome, characteristic facial features (acrogeria) in most patients, and by proneness to spontaneous rupture of bowel and large arteries. The vascular complications may affect all anatomical areas.^[2] ^[3] ^[4] ^[5] ^[6] ^[7] ^[8] ^[9] ^[10] ^[11] [:]^[12] ^[13] [:]^[14] ^[15] ^[16] ^[17] ^[18] ^[19] ^[20] ^[21] ^[22] ^[23] ^[24] ^[25] Defects in COL3A1 are a cause of susceptibility to aortic aneurysm abdominal (AAA) [MIM:100070. AAA is a common multifactorial disorder characterized by permanent dilation of the abdominal aorta, usually due to degenerative changes in the aortic wall. Histologically, AAA is characterized by signs of chronic inflammation, destructive remodeling of the extracellular matrix, and depletion of vascular smooth muscle cells.^[26] ^[27] ^[28]

Function

CO3A1_HUMAN Collagen type III occurs in most soft connective tissues along with type I collagen.

References

↑ Narcisi P, Richards AJ, Ferguson SD, Pope FM. A family with Ehlers-Danlos syndrome type III/articular hypermobility syndrome has a glycine 637 to serine substitution in type III collagen. Hum Mol Genet. 1994 Sep;3(9):1617-20. PMID:7833919
↑ Richards AJ, Lloyd JC, Narcisi P, Ward PN, Nicholls AC, De Paepe A, Pope FM. A 27-bp deletion from one allele of the type III collagen gene (COL3A1) in a large family with Ehlers-Danlos syndrome type IV. Hum Genet. 1992 Jan;88(3):325-30. PMID:1370809
↑ Richards A, Narcisi P, Lloyd J, Ferguson C, Pope FM. The substitution of glycine 661 by arginine in type III collagen produces mutant molecules with different thermal stabilities and causes Ehlers-Danlos syndrome type IV. J Med Genet. 1993 Aug;30(8):690-3. PMID:8411057
↑ Tromp G, Kuivaniemi H, Shikata H, Prockop DJ. A single base mutation that substitutes serine for glycine 790 of the alpha 1 (III) chain of type III procollagen exposes an arginine and causes Ehlers-Danlos syndrome IV. J Biol Chem. 1989 Jan 25;264(3):1349-52. PMID:2492273
↑ Tromp G, De Paepe A, Nuytinck L, Madhatheri S, Kuivaniemi H. Substitution of valine for glycine 793 in type III procollagen in Ehlers-Danlos syndrome type IV. Hum Mutat. 1995;5(2):179-81. PMID:7749417 doi:http://dx.doi.org/10.1002/humu.1380050213
↑ Richards AJ, Ward PN, Narcisi P, Nicholls AC, Lloyd JC, Pope FM. A single base mutation in the gene for type III collagen (COL3A1) converts glycine 847 to glutamic acid in a family with Ehlers-Danlos syndrome type IV. An unaffected family member is mosaic for the mutation. Hum Genet. 1992 Jun;89(4):414-8. PMID:1352273
↑ Tromp G, Kuivaniemi H, Stolle C, Pope FM, Prockop DJ. Single base mutation in the type III procollagen gene that converts the codon for glycine 883 to aspartate in a mild variant of Ehlers-Danlos syndrome IV. J Biol Chem. 1989 Nov 15;264(32):19313-7. PMID:2808425
↑ Richards AJ, Lloyd JC, Ward PN, De Paepe A, Narcisi P, Pope FM. Characterisation of a glycine to valine substitution at amino acid position 910 of the triple helical region of type III collagen in a patient with Ehlers-Danlos syndrome type IV. J Med Genet. 1991 Jul;28(7):458-63. PMID:1895316
↑ Johnson PH, Richards AJ, Pope FM, Hopkinson DA. A COL3A1 glycine 1006 to glutamic acid substitution in a patient with Ehlers-Danlos syndrome type IV detected by denaturing gradient gel electrophoresis. J Inherit Metab Dis. 1992;15(3):426-30. PMID:1357232
↑ Kontusaari S, Tromp G, Kuivaniemi H, Stolle C, Pope FM, Prockop DJ. Substitution of aspartate for glycine 1018 in the type III procollagen (COL3A1) gene causes type IV Ehlers-Danlos syndrome: the mutated allele is present in most blood leukocytes of the asymptomatic and mosaic mother. Am J Hum Genet. 1992 Sep;51(3):497-507. PMID:1496983
↑ Narcisi P, Wu Y, Tromp G, Earley JJ, Richards AJ, Pope FM, Kuivaniemi H. Single base mutation that substitutes glutamic acid for glycine 1021 in the COL3A1 gene and causes Ehlers-Danlos syndrome type IV. Am J Med Genet. 1993 May 15;46(3):278-83. PMID:8098182 doi:http://dx.doi.org/10.1002/ajmg.1320460308
↑ Madhatheri SL, Tromp G, Gustavson KH, Kuivaniemi H. Substitution of glutamic acid for glycine 589 in the triple-helical domain of type III procollagen (COL3A1) in a family with variable phenotype of the Ehlers-Danlos syndrome type IV. Hum Mol Genet. 1994 Mar;3(3):511-2. PMID:7912131
↑ Nuytinck L, De Paepe A, Renard JP, Adriaens F, Leroy J. Single-strand conformation polymorphism (SSCP) analysis of the COL3A1 gene detects a mutation that results in the substitution of glycine 1009 to valine and causes severe Ehlers-Danlos syndrome type IV. Hum Mutat. 1994;3(3):268-74. PMID:8019562 doi:http://dx.doi.org/10.1002/humu.1380030315
↑ Johnson PH, Richards AJ, Lloyd JC, Pope FM, Hopkinson DA. Efficient strategy for the detection of mutations in acrogeric Ehlers-Danlos syndrome type IV. Hum Mutat. 1995;6(4):336-42. PMID:8680408 doi:10.1002/humu.1380060408
↑ Mackay K, Raghunath M, Superti-Furga A, Steinmann B, Dalgleish R. Ehlers-Danlos syndrome type IV caused by Gly400Glu, Gly595Cys and Gly1003Asp substitutions in collagen III: clinical features, biochemical screening, and molecular confirmation. Clin Genet. 1996 Jun;49(6):286-95. PMID:8884076
↑ McGrory J, Weksberg R, Thorner P, Cole WG. Abnormal extracellular matrix in Ehlers-Danlos syndrome type IV due to the substitution of glycine 934 by glutamic acid in the triple helical domain of type III collagen. Clin Genet. 1996 Dec;50(6):442-5. PMID:9147870
↑ McGrory J, Costa T, Cole WG. A novel G499D substitution in the alpha 1(III) chain of type III collagen produces variable forms of Ehlers-Danlos syndrome type IV. Hum Mutat. 1996;7(1):59-60. PMID:8664902 doi:<59::AID-HUMU8>3.0.CO;2-K 10.1002/(SICI)1098-1004(1996)7:1<59::AID-HUMU8>3.0.CO;2-K
↑ Anderson DW, Thakker-Varia S, Tromp G, Kuivaniemi H, Stolle CA. A glycine (415)-to-serine substitution results in impaired secretion and decreased thermal stability of type III procollagen in a patient with Ehlers-Danlos syndrome type IV. Hum Mutat. 1997;9(1):62-3. PMID:8990011 doi:<62::AID-HUMU11>3.0.CO;2-N 10.1002/(SICI)1098-1004(1997)9:1<62::AID-HUMU11>3.0.CO;2-N
↑ Smith LT, Schwarze U, Goldstein J, Byers PH. Mutations in the COL3A1 gene result in the Ehlers-Danlos syndrome type IV and alterations in the size and distribution of the major collagen fibrils of the dermis. J Invest Dermatol. 1997 Mar;108(3):241-7. PMID:9036918
↑ Bateman JF, Chiodo AA, Weng YM, Chan D, Haan E. A type III collagen Gly559 to Arg helix mutation in Ehler's-Danlos syndrome type IV. Hum Mutat. 1998;Suppl 1:S257-9. PMID:9452103
↑ Giunta C, Steinmann B. Characterization of 11 new mutations in COL3A1 of individuals with Ehlers-Danlos syndrome type IV: preliminary comparison of RNase cleavage, EMC and DHPLC assays. Hum Mutat. 2000 Aug;16(2):176-7. PMID:10923041 doi:<176::AID-HUMU12>3.0.CO;2-E 10.1002/1098-1004(200008)16:2<176::AID-HUMU12>3.0.CO;2-E
↑ Pepin M, Schwarze U, Superti-Furga A, Byers PH. Clinical and genetic features of Ehlers-Danlos syndrome type IV, the vascular type. N Engl J Med. 2000 Mar 9;342(10):673-80. PMID:10706896
↑ Nishiyama Y, Nejima J, Watanabe A, Kotani E, Sakai N, Hatamochi A, Shinkai H, Kiuchi K, Tamura K, Shimada T, Takano T, Katayama Y. Ehlers-Danlos syndrome type IV with a unique point mutation in COL3A1 and familial phenotype of myocardial infarction without organic coronary stenosis. J Intern Med. 2001 Jan;249(1):103-8. PMID:11168790
↑ Kroes HY, Pals G, van Essen AJ. Ehlers-Danlos syndrome type IV: unusual congenital anomalies in a mother and son with a COL3A1 mutation and a normal collagen III protein profile. Clin Genet. 2003 Mar;63(3):224-7. PMID:12694234
↑ Palmeri S, Mari F, Meloni I, Malandrini A, Ariani F, Villanova M, Pompilio A, Schwarze U, Byers PH, Renieri A. Neurological presentation of Ehlers-Danlos syndrome type IV in a family with parental mosaicism. Clin Genet. 2003 Jun;63(6):510-5. PMID:12786757
↑ Tromp G, Wu Y, Prockop DJ, Madhatheri SL, Kleinert C, Earley JJ, Zhuang J, Norrgard O, Darling RC, Abbott WM, et al.. Sequencing of cDNA from 50 unrelated patients reveals that mutations in the triple-helical domain of type III procollagen are an infrequent cause of aortic aneurysms. J Clin Invest. 1993 Jun;91(6):2539-45. PMID:8514866 doi:http://dx.doi.org/10.1172/JCI116490
↑ Kontusaari S, Tromp G, Kuivaniemi H, Romanic AM, Prockop DJ. A mutation in the gene for type III procollagen (COL3A1) in a family with aortic aneurysms. J Clin Invest. 1990 Nov;86(5):1465-73. PMID:2243125 doi:http://dx.doi.org/10.1172/JCI114863
↑ Kontusaari S, Tromp G, Kuivaniemi H, Ladda RL, Prockop DJ. Inheritance of an RNA splicing mutation (G+ 1 IVS20) in the type III procollagen gene (COL3A1) in a family having aortic aneurysms and easy bruisability: phenotypic overlap between familial arterial aneurysms and Ehlers-Danlos syndrome type IV. Am J Hum Genet. 1990 Jul;47(1):112-20. PMID:2349939

1 Structural highlights
2 Disease
3 Function
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4gyx"

Categories: Homo sapiens | Large Structures | Bachinger HP | Boudko SP

@@ Line 3: / Line 3: @@
 <StructureSection load='4gyx' size='340' side='right'caption='[[4gyx]], [[Resolution|resolution]] 1.49&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4gyx]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4GYX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4GYX FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4gyx]] 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=4GYX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4GYX FirstGlance]. <br>
-</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=HYP:4-HYDROXYPROLINE'>HYP</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]] 1.49&#8491;</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=4gyx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gyx OCA], [http://pdbe.org/4gyx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4gyx RCSB], [http://www.ebi.ac.uk/pdbsum/4gyx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4gyx ProSAT]</span></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HYP:4-HYDROXYPROLINE'>HYP</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=4gyx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gyx OCA], [https://pdbe.org/4gyx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4gyx RCSB], [https://www.ebi.ac.uk/pdbsum/4gyx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4gyx ProSAT]</span></td></tr>
 </table>
-<div style="background-color:#fffaf0;">
+== Disease ==
-== Publication Abstract from PubMed ==
+[https://www.uniprot.org/uniprot/CO3A1_HUMAN CO3A1_HUMAN] Defects in COL3A1 are a cause of Ehlers-Danlos syndrome type 3 (EDS3) [MIM:[https://omim.org/entry/130020 130020]; also known as benign hypermobility syndrome. EDS is a connective tissue disorder characterized by hyperextensible skin, atrophic cutaneous scars due to tissue fragility and joint hyperlaxity. EDS3 is a form of Ehlers-Danlos syndrome characterized by marked joint hyperextensibility without skeletal deformity.<ref>PMID:7833919</ref>   Defects in COL3A1 are the cause of Ehlers-Danlos syndrome type 4 (EDS4) [MIM:[https://omim.org/entry/130050 130050]. EDS is a connective tissue disorder characterized by hyperextensible skin, atrophic cutaneous scars due to tissue fragility and joint hyperlaxity. EDS4 is the most severe form of the disease. It is characterized by the joint and dermal manifestations as in other forms of the syndrome, characteristic facial features (acrogeria) in most patients, and by proneness to spontaneous rupture of bowel and large arteries. The vascular complications may affect all anatomical areas.<ref>PMID:1370809</ref> <ref>PMID:8411057</ref> <ref>PMID:2492273</ref> <ref>PMID:7749417</ref> <ref>PMID:1352273</ref> <ref>PMID:2808425</ref> <ref>PMID:1895316</ref> <ref>PMID:1357232</ref> <ref>PMID:1496983</ref> <ref>PMID:8098182</ref> [:]<ref>PMID:7912131</ref> <ref>PMID:8019562</ref> [:]<ref>PMID:8680408</ref> <ref>PMID:8884076</ref> <ref>PMID:9147870</ref> <ref>PMID:8664902</ref> <ref>PMID:8990011</ref> <ref>PMID:9036918</ref> <ref>PMID:9452103</ref> <ref>PMID:10923041</ref> <ref>PMID:10706896</ref> <ref>PMID:11168790</ref> <ref>PMID:12694234</ref> <ref>PMID:12786757</ref>   Defects in COL3A1 are a cause of susceptibility to aortic aneurysm abdominal (AAA) [MIM:[https://omim.org/entry/100070 100070]. AAA is a common multifactorial disorder characterized by permanent dilation of the abdominal aorta, usually due to degenerative changes in the aortic wall. Histologically, AAA is characterized by signs of chronic inflammation, destructive remodeling of the extracellular matrix, and depletion of vascular smooth muscle cells.<ref>PMID:8514866</ref> <ref>PMID:2243125</ref> <ref>PMID:2349939</ref>
-Precise mapping and unraveling the mechanism of interaction or degradation of a certain type of collagen triple helix requires the generation of short and stable collagenous fragments. This is a great challenge especially for hetero-trimeric collagens, where chain composition and register (stagger) are important factors. No system has been reported that can be efficiently used to generate a natural collagenous fragment with exact chain composition and desired chain register. The NC2 domain (only 35-50 residues) of FACIT collagens is a potent trimerization domain. In case of type IX collagen it provides the efficient selection and hetero-trimerization of three distinct chains. The ability of the NC2 domain to determine the chain register of the triple helix is studied. We generated three possible sequence combinations (alpha1alpha1alpha2, alpha1alpha2alpha1, alpha2alpha1alpha1) of a type I collagen fragment (the binding region for the von Willebrand factor A3 domain) attached to the NC2 domain. In addition, two control combinations were produced that constitute homo-trimers of (alpha1)3 or (alpha2)3. For the hetero-trimeric constructs, alpha1alpha1alpha2 demonstrated a higher melting temperature than the other two. Binding experiments with the von Willebrand factor A3 domain revealed the homo-trimer of (alpha1)3 as the strongest binding construct, whereas the homo-trimer of (alpha2)3 showed no binding. For hetero-trimers, alpha1alpha1alpha2 was found to be the strongest binding construct. Differences in thermal stability and binding to the A3 domain unambiguously demonstrate that the NC2 domain of type IX collagen determines not only the chain composition but also the chain register of the adjacent triple helix.
+== Function ==
+[https://www.uniprot.org/uniprot/CO3A1_HUMAN CO3A1_HUMAN] Collagen type III occurs in most soft connective tissues along with type I collagen.
-The NC2 domain of type IX collagen determines the chain register of the triple helix.,Boudko SP, Bachinger HP J Biol Chem. 2012 Nov 6. PMID:23132862<ref>PMID:23132862</ref>
-From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-</div>
-<div class="pdbe-citations 4gyx" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Bachinger, H P]]
+[[Category: Bachinger HP]]
-[[Category: Boudko, S P]]
+[[Category: Boudko SP]]
-[[Category: 4-hydroxylation]]
-[[Category: Blood clotting]]
-[[Category: Collagen triple helix]]
-[[Category: Extracellular matrix]]
-[[Category: Structural protein]]
-[[Category: Type iii collagen cysteine knot]]
-[[Category: Von willebrand factor a3 domain]]

4gyx

From Proteopedia

Current revision

The von Willebrand Factor A3 domain binding region of type III collagen stabilized by the cysteine knot

Structural highlights

Disease

Function

References

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