Tuesday, 13 December, 2016

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

A. Kedrov, S. Wickles, A. H. Crevenna, E. O. van der Sluis, R. Buschauer, O. Berninghausen, D. C. Lamb and R. Beckmann -
Cell Reports, 10.1016/j.celrep.2016.11.059 (2016)

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.

Article on journal´s webpage