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'''Unreleased structure'''


The entry 3mql is ON HOLD
==Crystal structure of the fibronectin 6FnI1-2FnII7FnI fragment==
<StructureSection load='3mql' size='340' side='right'caption='[[3mql]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3mql]] is a 1 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=3MQL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3MQL FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.004&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene>, <scene name='pdbligand=MRD:(4R)-2-METHYLPENTANE-2,4-DIOL'>MRD</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=3mql FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3mql OCA], [https://pdbe.org/3mql PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3mql RCSB], [https://www.ebi.ac.uk/pdbsum/3mql PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3mql ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/FINC_HUMAN FINC_HUMAN] Defects in FN1 are the cause of glomerulopathy with fibronectin deposits type 2 (GFND2) [MIM:[https://omim.org/entry/601894 601894]; also known as familial glomerular nephritis with fibronectin deposits or fibronectin glomerulopathy. GFND is a genetically heterogeneous autosomal dominant disorder characterized clinically by proteinuria, microscopic hematuria, and hypertension that leads to end-stage renal failure in the second to fifth decade of life.<ref>PMID:18268355</ref>
== Function ==
[https://www.uniprot.org/uniprot/FINC_HUMAN FINC_HUMAN] Fibronectins bind cell surfaces and various compounds including collagen, fibrin, heparin, DNA, and actin. Fibronectins are involved in cell adhesion, cell motility, opsonization, wound healing, and maintenance of cell shape.<ref>PMID:8114919</ref> <ref>PMID:11209058</ref> <ref>PMID:15665290</ref> <ref>PMID:19379667</ref>  Anastellin binds fibronectin and induces fibril formation. This fibronectin polymer, named superfibronectin, exhibits enhanced adhesive properties. Both anastellin and superfibronectin inhibit tumor growth, angiogenesis and metastasis. Anastellin activates p38 MAPK and inhibits lysophospholipid signaling.<ref>PMID:8114919</ref> <ref>PMID:11209058</ref> <ref>PMID:15665290</ref> <ref>PMID:19379667</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/mq/3mql_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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=3mql ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Collagen and fibronectin (FN) are two abundant and essential components of the vertebrate extracellular matrix; they interact directly with cellular receptors and affect cell adhesion and migration. Past studies identified a FN fragment comprising six modules, (6)FnI(1-2)FnII(7-9)FnI, and termed the gelatin binding domain (GBD) as responsible for collagen interaction. Recently, we showed that the GBD binds tightly to a specific site within type I collagen and determined the structure of domains (8-9)FnI in complex with a peptide from that site. Here, we present the crystallographic structure of domains (6)FnI(1-2)FnII(7)FnI, which form a compact, globular unit through interdomain interactions. Analysis of NMR titrations with single-stranded collagen peptides reveals a dominant collagen interaction surface on domains (2)FnII and (7)FnI; a similar surface appears involved in interactions with triple-helical peptides. Models of the complete GBD, based on the new structure and the (8-9)FnI.collagen complex show a continuous putative collagen binding surface. We explore the implications of this model using long collagen peptides and discuss our findings in the context of FN interactions with collagen fibrils.


Authors: Erat, M.C., Campbell, I.D., Vakonakis, I.
Implications for collagen binding from the crystallographic structure of fibronectin 6FnI1-2FnII7FnI.,Erat MC, Schwarz-Linek U, Pickford AR, Farndale RW, Campbell ID, Vakonakis I J Biol Chem. 2010 Oct 29;285(44):33764-70. Epub 2010 Aug 24. PMID:20739283<ref>PMID:20739283</ref>


Description: Crystal structure of the fibronectin 6FnI1-2FnII7FnI fragment
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3mql" style="background-color:#fffaf0;"></div>


''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu May 20 09:18:05 2010''
==See Also==
*[[Fibronectin 3D structures|Fibronectin 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Campbell ID]]
[[Category: Erat MC]]
[[Category: Vakonakis I]]

Latest revision as of 12:26, 30 October 2024

Crystal structure of the fibronectin 6FnI1-2FnII7FnI fragmentCrystal structure of the fibronectin 6FnI1-2FnII7FnI fragment

Structural highlights

3mql is a 1 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 3.004Å
Ligands:, ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

FINC_HUMAN Defects in FN1 are the cause of glomerulopathy with fibronectin deposits type 2 (GFND2) [MIM:601894; also known as familial glomerular nephritis with fibronectin deposits or fibronectin glomerulopathy. GFND is a genetically heterogeneous autosomal dominant disorder characterized clinically by proteinuria, microscopic hematuria, and hypertension that leads to end-stage renal failure in the second to fifth decade of life.[1]

Function

FINC_HUMAN Fibronectins bind cell surfaces and various compounds including collagen, fibrin, heparin, DNA, and actin. Fibronectins are involved in cell adhesion, cell motility, opsonization, wound healing, and maintenance of cell shape.[2] [3] [4] [5] Anastellin binds fibronectin and induces fibril formation. This fibronectin polymer, named superfibronectin, exhibits enhanced adhesive properties. Both anastellin and superfibronectin inhibit tumor growth, angiogenesis and metastasis. Anastellin activates p38 MAPK and inhibits lysophospholipid signaling.[6] [7] [8] [9]

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

Collagen and fibronectin (FN) are two abundant and essential components of the vertebrate extracellular matrix; they interact directly with cellular receptors and affect cell adhesion and migration. Past studies identified a FN fragment comprising six modules, (6)FnI(1-2)FnII(7-9)FnI, and termed the gelatin binding domain (GBD) as responsible for collagen interaction. Recently, we showed that the GBD binds tightly to a specific site within type I collagen and determined the structure of domains (8-9)FnI in complex with a peptide from that site. Here, we present the crystallographic structure of domains (6)FnI(1-2)FnII(7)FnI, which form a compact, globular unit through interdomain interactions. Analysis of NMR titrations with single-stranded collagen peptides reveals a dominant collagen interaction surface on domains (2)FnII and (7)FnI; a similar surface appears involved in interactions with triple-helical peptides. Models of the complete GBD, based on the new structure and the (8-9)FnI.collagen complex show a continuous putative collagen binding surface. We explore the implications of this model using long collagen peptides and discuss our findings in the context of FN interactions with collagen fibrils.

Implications for collagen binding from the crystallographic structure of fibronectin 6FnI1-2FnII7FnI.,Erat MC, Schwarz-Linek U, Pickford AR, Farndale RW, Campbell ID, Vakonakis I J Biol Chem. 2010 Oct 29;285(44):33764-70. Epub 2010 Aug 24. PMID:20739283[10]

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

See Also

References

  1. ↑ Castelletti F, Donadelli R, Banterla F, Hildebrandt F, Zipfel PF, Bresin E, Otto E, Skerka C, Renieri A, Todeschini M, Caprioli J, Caruso RM, Artuso R, Remuzzi G, Noris M. Mutations in FN1 cause glomerulopathy with fibronectin deposits. Proc Natl Acad Sci U S A. 2008 Feb 19;105(7):2538-43. Epub 2008 Feb 11. PMID:18268355 doi:0707730105
  2. ↑ Morla A, Zhang Z, Ruoslahti E. Superfibronectin is a functionally distinct form of fibronectin. Nature. 1994 Jan 13;367(6459):193-6. PMID:8114919 doi:http://dx.doi.org/10.1038/367193a0
  3. ↑ Yi M, Ruoslahti E. A fibronectin fragment inhibits tumor growth, angiogenesis, and metastasis. Proc Natl Acad Sci U S A. 2001 Jan 16;98(2):620-4. PMID:11209058 doi:10.1073/pnas.98.2.620
  4. ↑ Ambesi A, Klein RM, Pumiglia KM, McKeown-Longo PJ. Anastellin, a fragment of the first type III repeat of fibronectin, inhibits extracellular signal-regulated kinase and causes G(1) arrest in human microvessel endothelial cells. Cancer Res. 2005 Jan 1;65(1):148-56. PMID:15665290
  5. ↑ You R, Klein RM, Zheng M, McKeown-Longo PJ. Regulation of p38 MAP kinase by anastellin is independent of anastellin's effect on matrix fibronectin. Matrix Biol. 2009 Mar;28(2):101-9. doi: 10.1016/j.matbio.2009.01.003. Epub 2009, Feb 4. PMID:19379667 doi:10.1016/j.matbio.2009.01.003
  6. ↑ Morla A, Zhang Z, Ruoslahti E. Superfibronectin is a functionally distinct form of fibronectin. Nature. 1994 Jan 13;367(6459):193-6. PMID:8114919 doi:http://dx.doi.org/10.1038/367193a0
  7. ↑ Yi M, Ruoslahti E. A fibronectin fragment inhibits tumor growth, angiogenesis, and metastasis. Proc Natl Acad Sci U S A. 2001 Jan 16;98(2):620-4. PMID:11209058 doi:10.1073/pnas.98.2.620
  8. ↑ Ambesi A, Klein RM, Pumiglia KM, McKeown-Longo PJ. Anastellin, a fragment of the first type III repeat of fibronectin, inhibits extracellular signal-regulated kinase and causes G(1) arrest in human microvessel endothelial cells. Cancer Res. 2005 Jan 1;65(1):148-56. PMID:15665290
  9. ↑ You R, Klein RM, Zheng M, McKeown-Longo PJ. Regulation of p38 MAP kinase by anastellin is independent of anastellin's effect on matrix fibronectin. Matrix Biol. 2009 Mar;28(2):101-9. doi: 10.1016/j.matbio.2009.01.003. Epub 2009, Feb 4. PMID:19379667 doi:10.1016/j.matbio.2009.01.003
  10. ↑ Erat MC, Schwarz-Linek U, Pickford AR, Farndale RW, Campbell ID, Vakonakis I. Implications for collagen binding from the crystallographic structure of fibronectin 6FnI1-2FnII7FnI. J Biol Chem. 2010 Oct 29;285(44):33764-70. Epub 2010 Aug 24. PMID:20739283 doi:10.1074/jbc.M110.139394

3mql, resolution 3.00Å

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