2goo

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spinqualitylabelsall models 2goo, resolution 2.2Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Ternary Complex of BMP-2 bound to BMPR-Ia-ECD and ActRII-ECD

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

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: Cowden-like syndrome OMIM:[601299], 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 NDG 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

Page seeded by OCA on Mon Nov 12 22:20:23 2007