Lanthanum ions inhibit the mammalian Sec61 complex in its channel dynamics and protein transport activity

Abstract

Previous electrophysiological experiments characterized the Sec61 complex, which provides the aqueous path for entry of newly-synthesized polypeptides into the mammalian endoplasmic reticulum, as a highly dynamic channel that, once activated by precursor proteins, fluctuates between main open states with mean conductances of 220 and 550 pS. Millimolar concentrations of lanthanum ions simultaneously restricted the dynamics of the Sec61 channel and inhibited translocation of polypeptides. Molecular modeling indicates that lanthanum binding sites cluster at the putative lateral gate of the Sec61 complex and suggests that structural flexibility of the lateral gate is essential for channel and protein transport activities of the Sec61 complex. (C) 2009 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.