+検索条件
-Structure paper
タイトル | Structure and Assembly Mechanism of the Signaling Complex Mediated by Human CSF-1. |
---|---|
ジャーナル・号・ページ | Structure, Vol. 23, Issue 9, Page 1621-1631, Year 2015 |
掲載日 | 2015年9月1日 |
著者 | Jan Felix / Steven De Munck / Kenneth Verstraete / Leander Meuris / Nico Callewaert / Jonathan Elegheert / Savvas N Savvides / |
PubMed 要旨 | Human colony-stimulating factor 1 receptor (hCSF-1R) is unique among the hematopoietic receptors because it is activated by two distinct cytokines, CSF-1 and interleukin-34 (IL-34). Despite ever- ...Human colony-stimulating factor 1 receptor (hCSF-1R) is unique among the hematopoietic receptors because it is activated by two distinct cytokines, CSF-1 and interleukin-34 (IL-34). Despite ever-growing insights into the central role of hCSF-1R signaling in innate and adaptive immunity, inflammatory diseases, and cancer, the structural basis of the functional dichotomy of hCSF-1R has remained elusive. Here, we report crystal structures of ternary complexes between hCSF-1 and hCSF-1R, including their complete extracellular assembly, and propose a mechanism for the cooperative human CSF-1:CSF-1R complex that relies on the adoption by dimeric hCSF-1 of an active conformational state and homotypic receptor interactions. Furthermore, we trace the cytokine-binding duality of hCSF-1R to a limited set of conserved interactions mediated by functionally equivalent residues on CSF-1 and IL-34 that play into the geometric requirements of hCSF-1R activation, and map the possible mechanistic consequences of somatic mutations in hCSF-1R associated with cancer. |
リンク | Structure / PubMed:26235028 |
手法 | SAS (X-ray synchrotron) / X線回折 |
解像度 | 2.802 - 6.853 Å |
構造データ | SASDAR6: PDB-4wrl: PDB-4wrm: |
化合物 | ChemComp-SIA: ChemComp-NAG: |
由来 |
|
キーワード | CYTOKINE/CYTOKINE RECEPTOR / cytokine-cytokine receptor complex |