4WRL

Structure of the human CSF-1:CSF-1R complex

4WRL の概要

• エントリーDOI: 10.2210/pdb4wrl/pdb
• 関連するBIRD辞書のPRD_ID: PRD_900067
• 分子名称: Macrophage colony-stimulating factor 1 receptor, Macrophage colony-stimulating factor 1, N-acetyl-alpha-neuraminic acid-(2-3)-beta-D-galactopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose, ... (7 entities in total)
• 機能のキーワード: cytokine-cytokine receptor complex, cytokine/cytokine receptor
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 107029.30

構造登録者

Felix, J.,De Munck, S.,Elegheert, J.,Savvides, S.N. (登録日: 2014-10-24, 公開日: 2015-08-12, 最終更新日: 2024-11-06)

主引用文献

Felix, J.,De Munck, S.,Verstraete, K.,Meuris, L.,Callewaert, N.,Elegheert, J.,Savvides, S.N.
Structure and Assembly Mechanism of the Signaling Complex Mediated by Human CSF-1.
Structure, 23:1621-1631, 2015

PubMed Abstract: 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.

PubMed: 26235028
DOI: 10.1016/j.str.2015.06.019

実験手法

X-RAY DIFFRACTION (2.802 Å)