| RRC ID |
10889
|
| 著者 |
Kotzsch A, Nickel J, Seher A, Sebald W, Müller TD.
|
| タイトル |
Crystal structure analysis reveals a spring-loaded latch as molecular mechanism for GDF-5-type I receptor specificity.
|
| ジャーナル |
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.
|
| 巻・号 |
28(7)
|
| ページ |
937-47
|
| 公開日 |
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
|
| 引用数 |
46
|
|
WOS 分野
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
CELL BIOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
ATDC5(RCB0565) |
