1Q8D

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

Summary for 1Q8D

• Entry DOI: 10.2210/pdb1q8d/pdb
• Descriptor: GDNF family receptor alpha 1, (4S)-2-METHYL-2,4-PENTANEDIOL (3 entities in total)
• Functional Keywords: all-alpha, cys-rich, hormone-growth factor receptor complex, hormone/growth factor receptor
• Biological source: Rattus norvegicus (Norway rat)
• Cellular location: Cell membrane; Lipid-anchor, GPI-anchor: Q62997
• Total number of polymer chains: 1
• Total formula weight: 12193.56

Authors

Leppanen, V.M.,Bespalov, M.M.,Runeberg-Roos, P.,Puurand, U.,Merits, A.,Saarma, M.,Goldman, A. (deposition date: 2003-08-21, release date: 2004-08-31, Last modification date: 2024-11-06)

Primary citation

Leppanen, V.M.,Bespalov, M.M.,Runeberg-Roos, P.,Puurand, U.,Merits, A.,Saarma, M.,Goldman, A.
The structure of GFRalpha1 domain 3 reveals new insights into GDNF binding and RET activation.
Embo J., 23:1452-1462, 2004

PubMed Abstract: 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.

PubMed: 15044950
DOI: 10.1038/sj.emboj.7600174

Experimental method

X-RAY DIFFRACTION (1.8 Å)