1GDF

STRUCTURE OF RHOGDI: A C-TERMINAL BINDING DOMAIN TARGETS AN N-TERMINAL INHIBITORY PEPTIDE TO GTPASES, NMR, MINIMIZED AVERAGE STRUCTURE

1GDF の概要

• エントリーDOI: 10.2210/pdb1gdf/pdb
• 分子名称: RHOGDI (1 entity in total)
• 機能のキーワード: rho-gtpase inhibitor, nucleotide exchange, isoprene binding
• 由来する生物種: Bos taurus (cattle)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 16708.01

構造登録者

Rosen, M.K.,Gosser, Y.Q. (登録日: 1997-05-11, 公開日: 1997-11-19, 最終更新日: 2024-05-22)

主引用文献

Gosser, Y.Q.,Nomanbhoy, T.K.,Aghazadeh, B.,Manor, D.,Combs, C.,Cerione, R.A.,Rosen, M.K.
C-terminal binding domain of Rho GDP-dissociation inhibitor directs N-terminal inhibitory peptide to GTPases.
Nature, 387:814-819, 1997

PubMed Abstract: The Rho GDP-dissociation inhibitors (GDIs) negatively regulate Rho-family GTPases. The inhibitory activity of GDI derives both from an ability to bind the carboxy-terminal isoprene of Rho family members and extract them from membranes, and from inhibition of GTPase cycling between the GTP- and GDP-bound states. Here we demonstrate that these binding and inhibitory functions of rhoGDI can be attributed to two structurally distinct regions of the protein. A carboxy-terminal folded domain of relative molecular mass 16,000 (M[r] 16K) binds strongly to the Rho-family member Cdc42, yet has little effect on the rate of nucleotide dissociation from the GTPase. The solution structure of this domain shows a beta-sandwich motif with a narrow hydrophobic cleft that binds isoprenes, and an exposed surface that interacts with the protein portion of Cdc42. The amino-terminal region of rhoGDI is unstructured in the absence of target and contributes little to binding, but is necessary to inhibit nucleotide dissociation from Cdc42. These results lead to a model of rhoGDI function in which the carboxy-terminal binding domain targets the amino-terminal inhibitory region to GTPases, resulting in membrane extraction and inhibition of nucleotide cycling.

PubMed: 9194563
DOI: 10.1038/42961

実験手法

SOLUTION NMR