A snapshot of membrane protein insertion

Abstract

The cytoplasm is the main place for protein translation from where nascent proteins are transported to their working areas, including the inside, outside, and membrane of the cell. The majority of newly synthesized membrane proteins is co-translationally inserted into the membrane by the evolutionary conserved Sec translocon. In this issue of EMBO Reports, Kater et al [1] use single-particle cryo-electron microscopy to visualize a high-resolution structure of the E. coli SecYEG translocon:ribosome-nascent chain complex in a lipid environment constituted by nanodiscs. This snapshot represents an early intermediate state in membrane protein insertion and provides important information for understanding the molecular mechanism of membrane protein biogenesis.

Figure 1. Cryo‐electron microscopy structure of the ribosome–Sec translocon complex in an early intermediate state

(A) Preparation of ribosome and Sec translocon to obtain an intermediate state of membrane protein insertion into the lipid bilayer. (Top) Translation of the fusion protein composed of the N‐terminal FtsQ TM region and TnaC, including an arrest sequence, is paused. (Bottom) SecYEG‐embedded nanodisc retains native‐like lipid environment. MSPs, membrane scaffold proteins. (B) The structure of SecYEG‐embedded nanodisc and ribosome‐nascent chain (RNC) complex using cryo‐electron microscopy. SecYEG represents an early intermediate state. The substrate map in the ribosome tunnel is identified. The substrate part outside of the ribosome is supposed to be located at the cytoplasmic side of the lateral gate. (C) Schematic representation of the quiescent state and the early intermediate state of SecYEG. Panels (B) and (C) are modified from Kater et al [1].