2goo
From Proteopedia
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'''Ternary Complex of BMP-2 bound to BMPR-Ia-ECD and ActRII-ECD''' | '''Ternary Complex of BMP-2 bound to BMPR-Ia-ECD and ActRII-ECD''' | ||
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[[Category: Allendorph, G P.]] | [[Category: Allendorph, G P.]] | ||
[[Category: Choe, S.]] | [[Category: Choe, S.]] | ||
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| - | [[Category: | + | [[Category: Alk-3]] |
| - | [[Category: | + | [[Category: Bmp-2]] |
| - | [[Category: | + | [[Category: Bmpr-ia]] |
| - | [[Category: | + | [[Category: Tgf-beta]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 05:20:43 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 02:20, 4 May 2008
Ternary Complex of BMP-2 bound to BMPR-Ia-ECD and ActRII-ECD
Contents |
Overview
The crystal structure of the complete signaling complex formed between bone morphogenetic protein 2 (BMP-2) and the extracellular domains (ECDs) of its type I receptor [bone morphogenetic protein receptor type Ia (BMPR-Ia)-ECD] and its type II receptor [activin receptor type II (ActRII)-ECD] shows two fundamental structural constraints for receptor assembly. First, the homodimeric BMP-2 ligand assembles two pairs of each receptor symmetrically, where each of the receptor ECDs does not make physical contact. Therefore, conformational communication between receptor ECDs, if any, should be propagated through the central ligand. Second, the type I and II receptor interfaces of the complex, when compared with those of binary complexes such as BMP-2/BMPR Ia-ECD, BMP-7/ActRII-ECD, and activin/ActRIIb-ECD, respectively, show there are common sets of positions repeatedly used by both ligands and receptors. Therefore, specificity-determining amino acid differences at the receptor interfaces should also account for the disparity in affinity of individual receptors for different ligand subunits. We find that a specific mutation to BMP-2 increases its affinity to ActRII-ECD by 5-fold. These results together establish that the specific signaling output is largely determined by two variables, the ligand-receptor pair identity and the mode of cooperative assembly of relevant receptors governed by the ligand flexibility in a membrane-restricted manner.
Disease
Known disease associated with this structure: HFE hemochromatosis, modifier of OMIM:[112261], Juvenile polyposis syndrome, infantile form OMIM:[601299], Polyposis syndrome, hereditary mixed, 2 OMIM:[601299], Polyposis, juvenile intestinal OMIM:[601299]
About this Structure
2GOO is a Protein complex structure of sequences from Homo sapiens and Mus musculus. Full crystallographic information is available from OCA.
Reference
Structure of the ternary signaling complex of a TGF-beta superfamily member., Allendorph GP, Vale WW, Choe S, Proc Natl Acad Sci U S A. 2006 May 16;103(20):7643-8. Epub 2006 May 3. PMID:16672363 Page seeded by OCA on Sun May 4 05:20:43 2008
