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

Erdmann, Frank; Jung, Martin; Eyrisch, Susanne; Lang, Sven; Helms, Volkhard; Wagner, Richard; Zimmermann, Richard

doi:10.1016/j.febslet.2009.06.032

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Volume 583, Issue 14 , Pages 2359-2364, 21 July 2009

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

Edited by Maurice Montal

Frank Erdmann
- Biophysik, Universität Osnabrück, FB Biologie/Chemie, D-49034 Osnabrück, Germany
Martin Jung
- Medical Biochemistry and Molecular Biology, Saarland University, D-66421 Homburg, Germany
Susanne Eyrisch
- Computational Biology, Saarland University, D-66041 Saarbrücken, Germany
Sven Lang
- Medical Biochemistry and Molecular Biology, Saarland University, D-66421 Homburg, Germany
Volkhard Helms
- Computational Biology, Saarland University, D-66041 Saarbrücken, Germany
Richard Wagner
- Biophysik, Universität Osnabrück, FB Biologie/Chemie, D-49034 Osnabrück, Germany
- Corresponding authors. Fax: +49 6841 1626288 (R. Zimmermann).
Richard Zimmermann
- Medical Biochemistry and Molecular Biology, Saarland University, D-66421 Homburg, Germany
- Corresponding authors. Fax: +49 6841 1626288 (R. Zimmermann).

Received 20 May 2009; received in revised form 16 June 2009; accepted 17 June 2009. published online 23 June 2009.

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 550pS. 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.