2ASE

NMR structure of the F28L mutant of Cdc42Hs

2ASE の概要

• エントリーDOI: 10.2210/pdb2ase/pdb
• 分子名称: Cell division control protein 42 homolog (1 entity in total)
• 機能のキーワード: gtp binding protein, g-protein, cell signalling, signaling protein
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cell membrane; Lipid-anchor; Cytoplasmic side (Potential): P60953
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 19740.69

構造登録者

Adams, P.D.,Oswald, R.E. (登録日: 2005-08-23, 公開日: 2006-02-21, 最終更新日: 2024-05-22)

主引用文献

Adams, P.D.,Oswald, R.E.
Solution Structure of an Oncogenic Mutant of Cdc42Hs
Biochemistry, 45:2577-2583, 2006

PubMed Abstract: Cdc42Hs(F28L) is a single-point mutant of Cdc42Hs, a member of the Ras superfamily of GTP-binding proteins, that facilitates cellular transformation brought about by an increased rate of cycling between GTP and GDP [Lin, R., et al. (1997) Curr. Biol. 7, 794-797]. Dynamics studies of Cdc42Hs(F28L)-GDP have shown increased flexibility for several residues at the nucleotide-binding site [Adams, P. D., et al. (2004) Biochemistry 43, 9968-9977]. The solution structure of Cdc42Hs-GDP (wild type) has previously been determined by NMR spectroscopy [Feltham, J. L., et al. (1997) Biochemistry 36, 8755-8766]. Here, we describe the solution structure of Cdc42Hs(F28L)-GDP, which provides insight into the structural basis for the change in affinity for GDP. Heteronuclear NMR experiments were performed to assign resonances in the protein, and distance, hydrogen bonding, residual dipolar coupling, and dihedral angle constraints were used to calculate a set of low-energy structures using distance geometry and simulated annealing refinement protocols. The overall structure of Cdc42Hs(F28L)-GDP is very similar to that of wild-type Cdc42Hs, consisting of a centrally located six-stranded beta-sheet structure surrounding the C-terminal alpha-helix [Feltham, J. L., et al. (1997) Biochemistry 36, 8755-8766]. In addition, the same three regions in wild-type Cdc42Hs that show structural disorder (Switch I, Switch II, and the Insert region) are disordered in F28L as well. Although the structure of Cdc42Hs(F28L)-GDP is very similar to that of the wild type, interactions with the nucleotide and hydrogen bonding within the nucleotide binding site are altered, and the region surrounding L28 is substantially more disordered.

PubMed: 16489751
DOI: 10.1021/bi051686g

実験手法

SOLUTION NMR