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1ry7
From Proteopedia
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| - | [[Image:1ry7.gif|left|200px]] | + | [[Image:1ry7.gif|left|200px]] |
| - | + | ||
| - | '''Crystal Structure of the 3 Ig form of FGFR3c in complex with FGF1''' | + | {{Structure |
| + | |PDB= 1ry7 |SIZE=350|CAPTION= <scene name='initialview01'>1ry7</scene>, resolution 3.20Å | ||
| + | |SITE= | ||
| + | |LIGAND= | ||
| + | |ACTIVITY= | ||
| + | |GENE= FGF1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), FGFR3c ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | }} | ||
| + | |||
| + | '''Crystal Structure of the 3 Ig form of FGFR3c in complex with FGF1''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1RY7 is a [ | + | 1RY7 is a [[Protein complex]] structure of sequences from [http://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]. |
==Reference== | ==Reference== | ||
| - | 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:[http:// | + | 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:[http://www.ncbi.nlm.nih.gov/pubmed/14732692 14732692] |
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
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[[Category: fgf-fgfr complex; beta trefoil; ig domain]] | [[Category: fgf-fgfr complex; beta trefoil; ig domain]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 13:57:51 2008'' |
Revision as of 11:57, 20 March 2008
| |||||||
| , resolution 3.20Å | |||||||
|---|---|---|---|---|---|---|---|
| Gene: | FGF1 (Homo sapiens), FGFR3c (Homo sapiens) | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal Structure of the 3 Ig form of FGFR3c in complex with FGF1
Contents |
Overview
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.
Disease
Known diseases associated with this structure: Achondroplasia OMIM:[134934], Aplasia of lacrimal and salivary glands OMIM:[602115], Bladder cancer OMIM:[134934], CATSHL syndrome OMIM:[134934], Cervical cancer, somatic OMIM:[134934], Colorectal cancer, somatic OMIM:[134934], Crouzon syndrome with acanthosis nigricans OMIM:[134934], Hypochondroplasia OMIM:[134934], LADD syndrome OMIM:[134934], LADD syndrome OMIM:[602115], Muenke syndrome OMIM:[134934], Nevus, keratinocytic, nonepidermolytic OMIM:[134934], Thanatophoric dysplasia, types I and II OMIM:[134934]
About this Structure
1RY7 is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
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
Page seeded by OCA on Thu Mar 20 13:57:51 2008
