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6hnf

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Revision as of 07:21, 31 October 2018

Structure in solution of human fibronectin type III-domain 14

Structural highlights

6hnf is a 1 chain structure with sequence from Human. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Gene:	FN1, FN (HUMAN)
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]

Publication Abstract from PubMed

Fibronectin is a large multi-domain protein of the extracellular matrix that harbors two heparin binding sites, Hep-I and Hep-II, which support the heparin-dependent adhesion of melanoma and neuroblastoma cells.1,2,3 The stronger heparin/HS binding site on fibronectin, Hep-II, spans across fibronectin type III-domains 12 to 14. Previous site-directed mutagenesis, NMR chemical shift perturbation, and crystallographic structural studies all agree in that the main heparin binding site is located on the surface of fibronectin type III domain 13.4,5 However, the 'synergy site' for heparin binding located on fibronectin type III domain 14 still remained elusive since actual binding sites could not be identified. Using NMR spectroscopy and ITC, we show here that heparin is able to bind to a cationic 'cradle' of fibronectin type III-domain 14 formed by the PRARI sequence, which is involved in the integrin a4beta1 interaction,5,6 and to the flexible loop comprising residues KNNQKSE between the last two beta sheets D and E of FN14. Our data reveal that the individual FN14 domain binds to the sulphated sugars Dp8 and Reviparin with similar affinities as the individual domain FN13 that contains the Hep-II site.7 Noteworthy, by introducing the last beta strand of FN13 and the linker region between type III-domains 13 and 14, the perturbation of NMR chemical shifts by heparin is significantly reduced, especially at the PRARI site. This indicates that the Hep-II binding site of fibronectin is mainly located on FN13 and the synergic binding site on FN14 only involves the KNNQKSE sequence.

Structure in solution of fibronectin type III-domain 14 reveals its synergistic heparin binding site.,Zhong X, Arnolds O, Krenczyk O, Gajewski J, Putz S, Herrmann C, Stoll R Biochemistry. 2018 Sep 27. doi: 10.1021/acs.biochem.8b00771. PMID:30260627^[10]

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

References

↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ 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
↑ Zhong X, Arnolds O, Krenczyk O, Gajewski J, Putz S, Herrmann C, Stoll R. Structure in solution of fibronectin type III-domain 14 reveals its synergistic heparin binding site. Biochemistry. 2018 Sep 27. doi: 10.1021/acs.biochem.8b00771. PMID:30260627 doi:http://dx.doi.org/10.1021/acs.biochem.8b00771

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/6hnf"

@@ Line 3: / Line 3: @@
 <StructureSection load='6hnf' size='340' side='right' caption='[[6hnf]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6hnf]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6HNF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6HNF FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6hnf]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6HNF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6HNF FirstGlance]. <br>
-</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=6hnf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6hnf OCA], [http://pdbe.org/6hnf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6hnf RCSB], [http://www.ebi.ac.uk/pdbsum/6hnf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6hnf ProSAT]</span></td></tr>
+</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">FN1, FN ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=6hnf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6hnf OCA], [http://pdbe.org/6hnf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6hnf RCSB], [http://www.ebi.ac.uk/pdbsum/6hnf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6hnf ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 23: / Line 24: @@
 __TOC__
 </StructureSection>
+[[Category: Human]]
 [[Category: Arnolds, O]]
 [[Category: Gajewski, J]]

6hnf

From Proteopedia

Revision as of 07:21, 31 October 2018

Structure in solution of human fibronectin type III-domain 14

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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