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Kedrov, Alexej; Wickles, Stephan; Crevenna, Alvaro H.; Sluis, Eli O. van der; Buschauer, Robert; Berninghausen, Otto; Lamb, Don C.; Beckmann, Roland (2016): Structural Dynamics of the YidC:Ribosome Complex during Membrane Protein Biogenesis. In: Cell Reports, Vol. 17, No. 11: pp. 2943-2954
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Abstract

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.