C-terminal binding domain of Rho GDP-dissociation inhibitor directs N- terminal inhibitory peptide to GTPases

Yuying Q. Gosser, Tyzoon K. Nomanbhoy, Behzad Aghazadeh, Danny Manor, Carolyn Combs, Richard A. Cerione, Michael K. Rosen

Research output: Contribution to journalArticlepeer-review

146 Scopus citations


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 β-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.

Original languageEnglish (US)
Pages (from-to)814-819
Number of pages6
Issue number6635
StatePublished - Jun 19 1997

ASJC Scopus subject areas

  • General


Dive into the research topics of 'C-terminal binding domain of Rho GDP-dissociation inhibitor directs N- terminal inhibitory peptide to GTPases'. Together they form a unique fingerprint.

Cite this