6hnf: Difference between revisions

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 6hnf is ON HOLD
+==Structure in solution of human fibronectin type III-domain 14==
+<StructureSection load='6hnf' size='340' side='right'caption='[[6hnf]]' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[6hnf]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. 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 [https://proteopedia.org/fgij/fg.htm?mol=6HNF FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=6hnf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6hnf OCA], [https://pdbe.org/6hnf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6hnf RCSB], [https://www.ebi.ac.uk/pdbsum/6hnf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6hnf 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>
+<div style="background-color:#fffaf0;">
+== 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.
-Authors: Zhong, X., Arnolds, O., Krenczyk, O., Gajewski, J., Puetz, S., Herrmann, C., Stoll, R.
+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<ref>PMID:30260627</ref>
-Description: Structure in solution of human fibronectin type III-domain 14
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Zhong, X]]
+<div class="pdbe-citations 6hnf" style="background-color:#fffaf0;"></div>
-[[Category: Herrmann, C]]
-[[Category: Krenczyk, O]]
+==See Also==
-[[Category: Arnolds, O]]
+*[[Fibronectin 3D structures|Fibronectin 3D structures]]
-[[Category: Stoll, R]]
+== References ==
-[[Category: Gajewski, J]]
+<references/>
-[[Category: Puetz, S]]
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Arnolds O]]
+[[Category: Gajewski J]]
+[[Category: Herrmann C]]
+[[Category: Krenczyk O]]
+[[Category: Puetz S]]
+[[Category: Stoll R]]
+[[Category: Zhong X]]