Cofactor-mediated conformational control in the bifunctional kinase/RNase Ire1.

ABSTRACT:

Background

Ire1 is a signal transduction protein in the endoplasmic reticulum (ER) membrane that serves to adjust the protein-folding capacity of the ER according to the needs of the cell. Ire1 signals, in a transcriptional program, the unfolded protein response (UPR) via the coordinated action of its protein kinase and RNase domains. In this study, we investigated how the binding of cofactors to the kinase domain of Ire1 modulates its RNase activity.

Results

Our results suggest that the kinase domain of Ire1 initially binds cofactors without activation of the RNase domain. RNase is activated upon a subsequent conformational rearrangement of Ire1 governed by the chemical properties of bound cofactors. The conformational step can be selectively inhibited by chemical perturbat

SUBMITTER: Korennykh AV 

PROVIDER: S-EPMC3158555 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature