2goo
From Proteopedia
(New page: 200px<br /> <applet load="2goo" size="450" color="white" frame="true" align="right" spinBox="true" caption="2goo, resolution 2.2Å" /> '''Ternary Complex of B...) |
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| - | [[Image:2goo.gif|left|200px]]<br /> | + | [[Image:2goo.gif|left|200px]]<br /><applet load="2goo" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="2goo" size=" | + | |
caption="2goo, resolution 2.2Å" /> | caption="2goo, resolution 2.2Å" /> | ||
'''Ternary Complex of BMP-2 bound to BMPR-Ia-ECD and ActRII-ECD'''<br /> | '''Ternary Complex of BMP-2 bound to BMPR-Ia-ECD and ActRII-ECD'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The crystal structure of the complete signaling complex formed between | + | 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== | ==Disease== | ||
| - | Known diseases associated with this structure: | + | Known diseases associated with this structure: HFE hemochromatosis, modifier of OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=112261 112261]], Juvenile polyposis syndrome, infantile form OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=601299 601299]], Polyposis syndrome, hereditary mixed, 2 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=601299 601299]], Polyposis, juvenile intestinal OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=601299 601299]] |
==About this Structure== | ==About this Structure== | ||
| - | 2GOO is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with NDG as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Receptor_protein_serine/threonine_kinase Receptor protein serine/threonine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.30 2.7.11.30] Full crystallographic information is available from [http:// | + | 2GOO is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with <scene name='pdbligand=NDG:'>NDG</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Receptor_protein_serine/threonine_kinase Receptor protein serine/threonine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.30 2.7.11.30] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2GOO OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Receptor protein serine/threonine kinase]] | [[Category: Receptor protein serine/threonine kinase]] | ||
| - | [[Category: Allendorph, G | + | [[Category: Allendorph, G P.]] |
[[Category: Choe, S.]] | [[Category: Choe, S.]] | ||
[[Category: NDG]] | [[Category: NDG]] | ||
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[[Category: tgf-beta]] | [[Category: tgf-beta]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:33:45 2008'' |
Revision as of 15:33, 21 February 2008
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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 diseases 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 with as ligand. Active as Receptor protein serine/threonine kinase, with EC number 2.7.11.30 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
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