Translocon

Membrane proteins with multiple transmembrane domains play critical roles in cell physiology, but little is translocon about the machinery coordinating their biogenesis at the endoplasmic reticulum, translocon.

J Cell Sci 1 February ; 3 : jcs The endoplasmic reticulum ER translocon complex is the main gate into the secretory pathway, facilitating the translocation of nascent peptides into the ER lumen or their integration into the lipid membrane. Protein biogenesis in the ER involves additional processes, many of them occurring co-translationally while the nascent protein resides at the translocon complex, including recruitment of ER-targeted ribosome—nascent-chain complexes, glycosylation, signal peptide cleavage, membrane protein topogenesis and folding. To perform such varied functions on a broad range of substrates, the ER translocon complex has different accessory components that associate with it either stably or transiently. Here, we review recent structural and functional insights into this dynamically constituted central hub in the ER and its components. Recent cryo-electron microscopy EM studies have dissected the molecular organization of the co-translational ER translocon complex, comprising the Sec61 protein-conducting channel, the translocon-associated protein complex and the oligosaccharyl transferase complex.

Translocon

The translocon also known as a translocator or translocation channel is a complex of proteins associated with the translocation of polypeptides across membranes. This translocation process requires the protein to cross a hydrophobic lipid bilayer. The same complex is also used to integrate nascent proteins into the membrane itself membrane proteins. In prokaryotes , a similar protein complex transports polypeptides across the inner plasma membrane or integrates membrane proteins. This article focuses on the cell's native translocons, but pathogens can also assemble other translocons in their host membranes, allowing them to export virulence factors into their target cells. The translocation channel is a hetero-trimeric protein complex called SecYEG in prokaryotes and Sec61 in eukaryotes. The structure of this channel, in its idle state, has been solved by X-ray crystallography in archaea. In a side view, the channel has an hourglass shape, with a funnel on each side. The extracellular funnel has a little "plug" formed out of an alpha-helix. In the middle of the membrane is a construction, formed from a pore ring of six hydrophobic amino acids that project their side chains inwards. During protein translocation, the plug is moved out of the way, and a polypeptide chain is moved from the cytoplasmic funnel, through the pore ring, the extracellular funnel, into the extracellular space. Hydrophobic segments of membrane proteins exit sideways through the lateral gate into the lipid phase and become membrane-spanning segments.

Structure of the mammalian oligosaccharyl-transferase complex in the native Translocon protein translocon.

Thank you for visiting nature. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser or turn off compatibility mode in Internet Explorer. In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript. In eukaryotic cells, one-third of all proteins must be transported across or inserted into the endoplasmic reticulum ER membrane by the ER protein translocon. The translocon-associated protein TRAP complex is an integral component of the translocon, assisting the Sec61 protein-conducting channel by regulating signal sequence and transmembrane helix insertion in a substrate-dependent manner. Here we use cryo-electron tomography CET to study the structure of the native translocon in evolutionarily divergent organisms and disease-linked TRAP mutant fibroblasts from human patients.

Thank you for visiting nature. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser or turn off compatibility mode in Internet Explorer. In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript. Chloroplasts rely on the translocon complexes in the outer and inner envelope membranes the TOC and TIC complexes, respectively to import thousands of different nuclear-encoded proteins from the cytosol 1 , 2 , 3 , 4. Although previous studies indicated that the TOC and TIC complexes may assemble into larger supercomplexes 5 , 6 , 7 , the overall architectures of the TOC—TIC supercomplexes and the mechanism of preprotein translocation are unclear. As the largest protein, Tic traverses the inner membrane, the intermembrane space and the outer membrane, connecting the TOC complex with the TIC proteins. An inositol hexaphosphate molecule is located at the Tic—Toc90 interface and stabilizes their assembly.

Translocon

The translocon also known as a translocator or translocation channel is a complex of proteins associated with the translocation of polypeptides across membranes. This translocation process requires the protein to cross a hydrophobic lipid bilayer. The same complex is also used to integrate nascent proteins into the membrane itself membrane proteins. In prokaryotes , a similar protein complex transports polypeptides across the inner plasma membrane or integrates membrane proteins. This article focuses on the cell's native translocons, but pathogens can also assemble other translocons in their host membranes, allowing them to export virulence factors into their target cells. The translocation channel is a hetero-trimeric protein complex called SecYEG in prokaryotes and Sec61 in eukaryotes. The structure of this channel, in its idle state, has been solved by X-ray crystallography in archaea. In a side view, the channel has an hourglass shape, with a funnel on each side. The extracellular funnel has a little "plug" formed out of an alpha-helix.

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We are grateful to Monika Lerner Homburg for excellent technical assistance. We assign positions to the four TRAP subunits in the assembled mammalian complex, providing new insights into membrane protein biogenesis and the role of TRAP in human congenital disorders of glycosylation. Anyone you share the following link with will be able to read this content:. Cryo-electron tomography: can it reveal the molecular sociology of cells in atomic detail? Methods 10 , — Sign in. Adam Frost. Thank you for visiting nature. The same complex is also used to integrate nascent proteins into the membrane itself membrane proteins. In addition to co-translational protein import and translocation, distinct ER translocon complexes enable post-translational translocation and membrane integration. TMCO1-ribosome complexes were isolated by centrifugation as before. Membrane proteins of the cell surface and most intracellular compartments are first assembled at the endoplasmic reticulum. Here, we review recent structural and mechanistic insights into the co- and post-translational ER translocon complex and the molecular principles that distinguish these modes. Where noted, maps were sharpened by applying a B-factor determined by the automated methods implemented in Relion3. In the post-translational mode, Sec61 forms a stable complex with the dimeric Sec62—Sec63 complex, and in fungi, additionally with Sec71 and Sec72 Deshaies et al.

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These points are unambiguous, even in the absence of TMCO1 side chain density, and they lead us to propose that the TMCO1 translocon functions as an insertase and an intramembrane chaperone. Despite decades of work, however, much less is known about how multi-pass proteins that span the membrane multiple times are made. In this case, the reviewers felt that one issue could be dealt with textually but they required one additional experiment be carried out prior to formal acceptance. Supplementary information Supplementary information - pdf file. Isolation of ribosome-associated membrane proteins RAMPs from solubilized pancreatic microsomes provided clues about the molecular composition of the ER translocon complex. Here, the large luminal domain of Nicalin extends into low-resolution density directly below the translocon Figure 2D. One of the classes from this classification showed strong density for the TMCO1 translocon 82, particles, ISBN Article PubMed Google Scholar. These changes in functional state are accompanied by structural rearrangements that alter translocon conformation, composition, and interactions with ligands such as the ribosome and BiP. Together with the structural analysis, these data implicate the TMCO1 translocon in multi-pass membrane protein biogenesis.