Reference - Detail
| RRC ID | 10889 |
|---|---|
| Author | Kotzsch A, Nickel J, Seher A, Sebald W, Müller TD. |
| Title | Crystal structure analysis reveals a spring-loaded latch as molecular mechanism for GDF-5-type I receptor specificity. |
| Journal | EMBO J |
| Abstract |
Dysregulation of growth and differentiation factor 5 (GDF-5) signalling, a member of the TGF-beta superfamily, is strongly linked to skeletal malformation. GDF-5-mediated signal transduction involves both BMP type I receptors, BMPR-IA and BMPR-IB. However, mutations in either GDF-5 or BMPR-IB lead to similar phenotypes, indicating that in chondrogenesis GDF-5 signalling seems to be exclusively mediated through BMPR-IB. Here, we present structural insights into the GDF-5:BMPR-IB complex revealing how binding specificity for BMPR-IB is generated on a molecular level. In BMPR-IB, a loop within the ligand-binding epitope functions similar to a latch allowing high-affinity binding of GDF-5. In BMPR-IA, this latch is in a closed conformation leading to steric repulsion. The new structural data now provide also a molecular basis of how phenotypically relevant missense mutations in GDF-5 might impair receptor binding and activation. |
| Volume | 28(7) |
| Pages | 937-47 |
| Published | 2009-4-8 |
| DOI | 10.1038/emboj.2009.37 |
| PII | emboj200937 |
| PMID | 19229295 |
| PMC | PMC2670865 |
| MeSH | Binding Sites Bone Morphogenetic Protein Receptors, Type I / chemistry Bone Morphogenetic Protein Receptors, Type I / metabolism* Cell Line, Tumor Crystallography, X-Ray Growth Differentiation Factor 5 / chemistry* Growth Differentiation Factor 5 / metabolism Humans Models, Molecular Mutation Protein Conformation Sensitivity and Specificity |
| IF | 9.889 |
| Times Cited | 46 |
| WOS Category | BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | Patent(IFI CLAIMS) |
| Total number of mentions | 7 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | ATDC5(RCB0565) |