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{{STRUCTURE_2fn2|  PDB=2fn2  |  SCENE=  }}
==SOLUTION NMR STRUCTURE OF THE GLYCOSYLATED SECOND TYPE TWO MODULE OF FIBRONECTIN, 20 STRUCTURES==
===SOLUTION NMR STRUCTURE OF THE GLYCOSYLATED SECOND TYPE TWO MODULE OF FIBRONECTIN, 20 STRUCTURES===
<StructureSection load='2fn2' size='340' side='right' caption='[[2fn2]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
{{ABSTRACT_PUBMED_9514732}}
== Structural highlights ==
<table><tr><td colspan='2'>[[2fn2]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2FN2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2FN2 FirstGlance]. <br>
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene><br>
<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2fn2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2fn2 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2fn2 RCSB], [http://www.ebi.ac.uk/pdbsum/2fn2 PDBsum]</span></td></tr>
<table>
== Disease ==
[[http://www.uniprot.org/uniprot/FINC_HUMAN FINC_HUMAN]] Defects in FN1 are the cause of glomerulopathy with fibronectin deposits type 2 (GFND2) [MIM:[http://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 ==
[[http://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/fn/2fn2_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.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/chain_selection.php?pdb_ID=2ata ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Fibronectin is an extracellular matrix glycoprotein that plays a role in a number of physiological processes involving cell adhesion and migration. The modules of the fibronectin monomer are organized into proteolytically resistant domains that in isolation retain their affinity for various ligands. The tertiary structure of the glycosylated second type 2 module (2F2) from the gelatin-binding domain of fibronectin was determined by two-dimensional nuclear magnetic resonance spectroscopy and simulated annealing. The structure is well defined with an overall fold typical of F2 modules, showing two double-stranded antiparallel beta-sheets and a partially solvent-exposed hydrophobic cluster. An N-terminal beta-sheet, that was not present in previously determined F2 module structures, may be important for defining the relative orientation of adjacent F2 modules in fibronectin. This is the first three-dimensional structure of a glycosylated module of fibronectin, and provides insight into the possible role of the glycosylation in protein stability, protease resistance and modulation of collagen binding. Based on the structures of the isolated modules, models for the 1F22F2 pair were generated by randomly changing the orientation of the linker peptide between the modules. The models suggest that the two putative collagen binding sites in the pair form discrete binding sites, rather than combining to form a single binding site.


==Disease==
Solution structure of the glycosylated second type 2 module of fibronectin.,Sticht H, Pickford AR, Potts JR, Campbell ID J Mol Biol. 1998 Feb 13;276(1):177-87. PMID:9514732<ref>PMID:9514732</ref>
[[http://www.uniprot.org/uniprot/FINC_HUMAN FINC_HUMAN]] Defects in FN1 are the cause of glomerulopathy with fibronectin deposits type 2 (GFND2) [MIM:[http://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==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[http://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>  
</div>
 
==About this Structure==
[[2fn2]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2FN2 OCA].


==See Also==
==See Also==
*[[Fibronectin|Fibronectin]]
*[[Fibronectin|Fibronectin]]
 
== References ==
==Reference==
<references/>
<ref group="xtra">PMID:009514732</ref><ref group="xtra">PMID:012856000</ref><references group="xtra"/><references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Campbell, I D.]]
[[Category: Campbell, I D.]]

Revision as of 11:14, 30 September 2014

SOLUTION NMR STRUCTURE OF THE GLYCOSYLATED SECOND TYPE TWO MODULE OF FIBRONECTIN, 20 STRUCTURESSOLUTION NMR STRUCTURE OF THE GLYCOSYLATED SECOND TYPE TWO MODULE OF FIBRONECTIN, 20 STRUCTURES

Structural highlights

2fn2 is a 1 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Resources:FirstGlance, OCA, RCSB, PDBsum

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

Fibronectin is an extracellular matrix glycoprotein that plays a role in a number of physiological processes involving cell adhesion and migration. The modules of the fibronectin monomer are organized into proteolytically resistant domains that in isolation retain their affinity for various ligands. The tertiary structure of the glycosylated second type 2 module (2F2) from the gelatin-binding domain of fibronectin was determined by two-dimensional nuclear magnetic resonance spectroscopy and simulated annealing. The structure is well defined with an overall fold typical of F2 modules, showing two double-stranded antiparallel beta-sheets and a partially solvent-exposed hydrophobic cluster. An N-terminal beta-sheet, that was not present in previously determined F2 module structures, may be important for defining the relative orientation of adjacent F2 modules in fibronectin. This is the first three-dimensional structure of a glycosylated module of fibronectin, and provides insight into the possible role of the glycosylation in protein stability, protease resistance and modulation of collagen binding. Based on the structures of the isolated modules, models for the 1F22F2 pair were generated by randomly changing the orientation of the linker peptide between the modules. The models suggest that the two putative collagen binding sites in the pair form discrete binding sites, rather than combining to form a single binding site.

Solution structure of the glycosylated second type 2 module of fibronectin.,Sticht H, Pickford AR, Potts JR, Campbell ID J Mol Biol. 1998 Feb 13;276(1):177-87. PMID:9514732[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. ↑ Sticht H, Pickford AR, Potts JR, Campbell ID. Solution structure of the glycosylated second type 2 module of fibronectin. J Mol Biol. 1998 Feb 13;276(1):177-87. PMID:9514732 doi:10.1006/jmbi.1997.1528
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