1Q8D

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

1Q8D の概要

• エントリーDOI: 10.2210/pdb1q8d/pdb
• 分子名称: GDNF family receptor alpha 1, (4S)-2-METHYL-2,4-PENTANEDIOL (3 entities in total)
• 機能のキーワード: all-alpha, cys-rich, hormone-growth factor receptor complex, hormone/growth factor receptor
• 由来する生物種: Rattus norvegicus (Norway rat)
• 細胞内の位置: Cell membrane; Lipid-anchor, GPI-anchor: Q62997
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 12193.56

構造登録者

Leppanen, V.M.,Bespalov, M.M.,Runeberg-Roos, P.,Puurand, U.,Merits, A.,Saarma, M.,Goldman, A. (登録日: 2003-08-21, 公開日: 2004-08-31, 最終更新日: 2024-11-06)

主引用文献

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

実験手法

X-RAY DIFFRACTION (1.8 Å)