1q8d

The crystal structure of GDNF family co-receptor alpha 1 domain 3

spinqualitylabelsall models 1q8d, resolution 1.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1q8d is a 1 chain structure with sequence from Rattus norvegicus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.8Å Ligands: MPD, MSE Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function GFRA1_RAT Receptor for GDNF. Mediates the GDNF-induced autophosphorylation and activation of the RET receptor. 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 PubMed Glial cell line-derived neurotrophic factor (GDNF) binds to the GDNF family co-receptor alpha1 (GFRalpha1) and activates RET receptor tyrosine kinase. GFRalpha1 has a putative domain structure of three homologous cysteine-rich domains, where domains 2 and 3 make up a central domain responsible for GDNF binding. We report here the 1.8 A crystal structure of GFRalpha1 domain 3 showing a new protein fold. It is an all-alpha five-helix bundle with five disulfide bridges. The structure was used to model the homologous domain 2, the other half of the GDNF-binding fragment, and to construct the first structural model of the GDNF-GFRalpha1 interaction. Using site-directed mutagenesis, we identified closely spaced residues, Phe213, Arg224, Arg225 and Ile229, comprising a putative GDNF-binding surface. Mutating each one of them had slightly different effects on GDNF binding and RET phosphorylation. In addition, the R217E mutant bound GDNF equally well in the presence and absence of RET. Arg217 may thus be involved in the allosteric properties of GFRalpha1 or in binding RET. The structure of GFRalpha1 domain 3 reveals new insights into GDNF binding and RET activation.,Leppanen VM, Bespalov MM, Runeberg-Roos P, Puurand U, Merits A, Saarma M, Goldman A EMBO J. 2004 Apr 7;23(7):1452-62. Epub 2004 Mar 25. PMID:15044950 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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