1ry7: Difference between revisions
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==Crystal Structure of the 3 Ig form of FGFR3c in complex with FGF1== | |||
<StructureSection load='1ry7' size='340' side='right'caption='[[1ry7]], [[Resolution|resolution]] 3.20Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[1ry7]] is a 2 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=1RY7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1RY7 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]] 3.2Å</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=1ry7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ry7 OCA], [https://pdbe.org/1ry7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ry7 RCSB], [https://www.ebi.ac.uk/pdbsum/1ry7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ry7 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/FGF1_HUMAN FGF1_HUMAN] Plays an important role in the regulation of cell survival, cell division, angiogenesis, cell differentiation and cell migration. Functions as potent mitogen in vitro.<ref>PMID:8663044</ref> <ref>PMID:16597617</ref> <ref>PMID:20145243</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/ry/1ry7_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=1ry7 ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The prototypical fibroblast growth factor receptor (FGFR) extracellular domain consists of three Ig domains (D1-D3) of which the two membrane-proximal D2 and D3 domains and the interconnecting D2-D3 linker bear the determinants of ligand binding and specificity. In contrast, D1 and the D1-D2 linker are thought to play autoinhibitory roles in FGFR regulation. Here, we report the crystal structure of the three-Ig form of FGFR3c in complex with FGF1, an FGF that binds promiscuously to each of the seven principal FGFRs. In this structure, D1 and the D1-D2 linker are completely disordered, demonstrating that these regions are dispensable for FGF binding. Real-time binding experiments using surface plasmon resonance show that relative to two-Ig form, the three-Ig form of FGFR3c exhibits lower affinity for both FGF1 and heparin. Importantly, we demonstrate that this autoinhibition is mediated by intramolecular interactions of D1 and the D1-D2 linker with the minimal FGF and heparin-binding D2-D3 region. As in the FGF1-FGFR2c structure, but not the FGF1-FGFR1c structure, the alternatively spliced betaC'-betaE loop is ordered and interacts with FGF1 in the FGF1-FGFR3c structure. However, in contrast to the FGF1-FGFR2c structure in which the betaC'-betaE loop interacts with the beta-trefoil core region of FGF1, in the FGF1-FGFR3c structure, this loop interacts extensively with the N-terminal region of FGF1, underscoring the importance of the FGF1 N terminus in conferring receptor-binding affinity and promiscuity. Importantly, comparison of the three FGF1-FGFR structures shows that the flexibility of the betaC'-betaE loop is a major determinant of ligand-binding specificity and promiscuity. | |||
Insights into the molecular basis for fibroblast growth factor receptor autoinhibition and ligand-binding promiscuity.,Olsen SK, Ibrahimi OA, Raucci A, Zhang F, Eliseenkova AV, Yayon A, Basilico C, Linhardt RJ, Schlessinger J, Mohammadi M Proc Natl Acad Sci U S A. 2004 Jan 27;101(4):935-40. Epub 2004 Jan 19. PMID:14732692<ref>PMID:14732692</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 1ry7" style="background-color:#fffaf0;"></div> | |||
== | ==See Also== | ||
[[ | *[[Fibroblast growth factor 3D structures|Fibroblast growth factor 3D structures]] | ||
*[[Fibroblast growth factor receptor 3D receptor|Fibroblast growth factor receptor 3D receptor]] | |||
== | == References == | ||
< | <references/> | ||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Basilico | [[Category: Large Structures]] | ||
[[Category: Eliseenkova | [[Category: Basilico C]] | ||
[[Category: Ibrahimi | [[Category: Eliseenkova AV]] | ||
[[Category: Linhardt | [[Category: Ibrahimi OA]] | ||
[[Category: Mohammadi | [[Category: Linhardt RJ]] | ||
[[Category: Olsen | [[Category: Mohammadi M]] | ||
[[Category: Raucci | [[Category: Olsen SK]] | ||
[[Category: Schlessinger | [[Category: Raucci A]] | ||
[[Category: Yayon | [[Category: Schlessinger J]] | ||
[[Category: Zhang | [[Category: Yayon A]] | ||
[[Category: Zhang F]] | |||
