1c8p | pdb_00001c8p
NMR STRUCTURE OF THE LIGAND BINDING DOMAIN OF THE COMMON BETA-CHAIN IN THE GM-CSF, IL-3 AND IL-5 RECEPTORS
Structural highlights
DiseaseIL3RB_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] FunctionIL3RB_HUMAN High affinity receptor for interleukin-3, interleukin-5 and granulocyte-macrophage colony-stimulating factor. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe haemopoietic cytokines, granulocyte-macrophage colony-stimulating factor, interleukin-3 and interleukin-5 bind to cell-surface receptors comprising ligand-specific alpha-chains and a shared beta-chain. The beta-chain is the critical signalling subunit of the receptor and its fourth domain not only plays a critical role in interactions with ligands, hence in receptor activation, but also contains residues whose mutation can lead to ligand-independent activation of the receptor. We have determined the NMR solution structure of the isolated human fourth domain of the beta-chain. The protein has a fibronectin type III fold with a well-defined hydrophobic core and is stabilised by an extensive network of pi-cation interactions involving Trp and Arg side-chains, including two Trp residues outside the highly conserved Trp-Ser-Xaa-Trp-Ser motif (where Xaa is any amino acid) that is found in many cytokine receptors. Most of the residues implicated in factor-independent mutants localise to the rigid core of the domain or the pi-cation stack. The loops between the B and C, and the F and G strands, that contain residues important for interactions with cytokines, lie adjacent at the membrane-distal end of the domain, consistent with their being involved cooperatively in binding cytokines. The elucidation of the structure of the cytokine-binding domain of the beta-chain provides insight into the cytokine-dependent and factor-independent activation of the receptor. The solution structure of the cytokine-binding domain of the common beta-chain of the receptors for granulocyte-macrophage colony-stimulating factor, interleukin-3 and interleukin-5.,Mulhern TD, Lopez AF, D'Andrea RJ, Gaunt C, Vandeleur L, Vadas MA, Booker GW, Bagley CJ J Mol Biol. 2000 Apr 7;297(4):989-1001. PMID:10736232[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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