Structural Dynamics of the YidC:Ribosome Complex during Membrane Protein Biogenesis

Publication date: 13 December 2016
Source:Cell Reports, Volume 17, Issue 11
Author(s): Alexej Kedrov, Stephan Wickles, Alvaro H. Crevenna, Eli O. van der Sluis, Robert Buschauer, Otto Berninghausen, Don C. Lamb, Roland Beckmann
Members of the YidC/Oxa1/Alb3 family universally facilitate membrane protein biogenesis, via mechanisms that have thus far remained unclear. Here, we investigated two crucial functional aspects: the interaction of YidC with ribosome:nascent chain complexes (RNCs) and the structural dynamics of RNC-bound YidC in nanodiscs. We observed that a fully exposed nascent transmembrane domain (TMD) is required for high-affinity YidC:RNC interactions, while weaker binding may already occur at earlier stages of translation. YidC efficiently catalyzed the membrane insertion of nascent TMDs in both fluid and gel phase membranes. Cryo-electron microscopy and fluorescence analysis revealed a conformational change in YidC upon nascent chain insertion: the essential TMDs 2 and 3 of YidC were tilted, while the amphipathic helix EH1 relocated into the hydrophobic core of the membrane. We suggest that EH1 serves as a mechanical lever, facilitating a coordinated movement of YidC TMDs to trigger the release of nascent chains into the membrane.

Graphical abstract

Teaser

Kedrov et al. use a combination of biochemical, biophysical, and structural approaches to study the insertase YidC in its native lipid environment upon interaction with ribosomes. The results describe how YidC recognizes translating ribosomes and changes its conformation upon nascent chain insertion.


http://ift.tt/2gZyIak