4nkq
From Proteopedia
Structure of a Cytokine Receptor Complex
Structural highlights
Disease[IL3RB_HUMAN] Defects in CSF2RB are the cause of pulmonary surfactant metabolism dysfunction type 5 (SMDP5) [MIM:614370]. SMDP5 is a rare lung disorder due to impaired surfactant homeostasis. It is characterized by alveolar filling with floccular material that stains positive using the periodic acid-Schiff method and is derived from surfactant phospholipids and protein components. Excessive lipoproteins accumulation in the alveoli results in severe respiratory distress.[1] [CSF2R_HUMAN] Defects in CSF2RA are the cause of pulmonary surfactant metabolism dysfunction type 4 (SMDP4) [MIM:300770]. A rare lung disorder due to impaired surfactant homeostasis. It is characterized by alveolar filling with floccular material that stains positive using the periodic acid-Schiff method and is derived from surfactant phospholipids and protein components. Excessive lipoproteins accumulation in the alveoli results in severe respiratory distress.[2] [3] Function[IL3RB_HUMAN] High affinity receptor for interleukin-3, interleukin-5 and granulocyte-macrophage colony-stimulating factor. [CSF2R_HUMAN] Low affinity receptor for granulocyte-macrophage colony-stimulating factor. Transduces a signal that results in the proliferation, differentiation, and functional activation of hematopoietic cells. [CSF2_HUMAN] Cytokine that stimulates the growth and differentiation of hematopoietic precursor cells from various lineages, including granulocytes, macrophages, eosinophils and erythrocytes. Publication Abstract from PubMedThe GM-CSF, IL-3, and IL-5 receptors constitute the betac family, playing important roles in inflammation, autoimmunity, and cancer. Typical of heterodimeric type I cytokine receptors, signaling requires recruitment of the shared subunit to the initial cytokine:alpha subunit binary complex through an affinity conversion mechanism. This critical process is poorly understood due to the paucity of crystal structures of both binary and ternary receptor complexes for the same cytokine. We have now solved the structure of the binary GM-CSF:GMRalpha complex at 2.8-A resolution and compared it with the structure of the ternary complex, revealing distinct conformational changes. Guided by these differences we performed mutational and functional studies that, importantly, show GMRalpha interactions playing a major role in receptor signaling while betac interactions control high-affinity binding. These results support the notion that conformational changes underlie the mechanism of GM-CSF receptor activation and also suggest how related type I cytokine receptors signal. Conformational Changes in the GM-CSF Receptor Suggest a Molecular Mechanism for Affinity Conversion and Receptor Signaling.,Broughton SE, Hercus TR, Nero TL, Dottore M, McClure BJ, Dhagat U, Taing H, Gorman MA, King-Scott J, Lopez AF, Parker MW Structure. 2016 Jul 6. pii: S0969-2126(16)30124-1. doi:, 10.1016/j.str.2016.05.017. PMID:27396825[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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