Molecular basis of the TRAP complex function in ER protein biogenesis
Open accessPublished version of a preprint
Abstract
The translocon-associated protein (TRAP) complex resides in the endoplasmic reticulum (ER) membrane and interacts with the Sec translocon and the ribosome to facilitate biogenesis of secretory and membrane proteins. TRAP plays a key role in the secretion of many hormones, including insulin. Here we reveal the molecular architecture of the mammalian TRAP complex and how it engages the translating ribosome associated with Sec61 translocon on the ER membrane. The TRAP complex is anchored to the ribosome via a long tether and its position is further stabilized by a finger-like loop. This positions a cradle-like lumenal domain of TRAP below the translocon for interactions with translocated nascent chains. Our structure-guided TRAP mutations in Caenorhabditis elegans lead to growth deficits associated with increased ER stress and defects in protein hormone secretion. These findings elucidate the molecular basis of the TRAP complex in the biogenesis and translocation of proteins at the ER.
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Highly accurate protein structure prediction with AlphaFold
Jumper, J., Evans, R., Pritzel, A., Green, T., Figurnov, M., Ronneberger, O., Tunyasuvunakool, K., Bates, R., Žídek, A., Potapenko, A., et al. (2021) · Nature · doi:10.1038/s41586-021-03819-2 · Cited by 43,764 · see citing works
ColabFold - Making protein folding accessible to all
Mirdita, M., Schütze, K., Moriwaki, Y., Heo, L., Ovchinnikov, S., & Steinegger, M. (2021) · doi:10.1101/2021.08.15.456425 · Cited by 9,391 · see citing works
Protein complex prediction with AlphaFold-Multimer
Evans, R., O’Neill, M., Pritzel, A., Antropova, N., Senior, A., Green, T., Žídek, A., Bates, R., Blackwell, S., Yim, J., et al. (2021) · doi:10.1101/2021.10.04.463034 · Cited by 3,808 · see citing works
Khalifa, A. A. Z., Ichikawa, M., Dai, D., Kubo, S., Black, C. S., Peri, K., McAlear, T. S., Veyron, S., Yang, S. K., Vargas, J., et al. (2020) · eLife · doi:10.7554/elife.52760 · Cited by 1,676 · see citing works
DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium, Mahajan, A., Asian Genetic Epidemiology Network Type 2 Diabetes (AGEN-T2D) Consortium, South Asian Type 2 Diabetes (SAT2D) Consortium, Mexican American Type 2 Diabetes (MAT2D) Consortium, Type 2 Diabetes Genetic Exploration by Next-generation sequencing in multi-Ethnic Samples (T2D-GENES) Consortium, Go, M. J., Zhang, W., Below, J. E., Gaulton, K. J., et al. (2014) · Nature Genetics · doi:10.1038/ng.2897 · Cited by 1,034 · see citing works
Structure of a complex of the ATPase SecA and the protein-translocation channel.
Zimmer, J., Nam, Y., & Rapoport, T. A. (2008) · Nature · doi:10.1038/nature07335 · Cited by 459 · see citing works
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- Authors
- Jaskolowski, M., Jomaa, A., Gamerdinger, M., Shrestha, S., Leibundgut, M., Deuerling, E., & Ban, N.
- Affiliations
- ETH Zurich (CH)
- University of Konstanz (DE)
- Corresponding author
- Jomaa, Ahmad
- Deuerling, Elke
- Ban, Nenad
- ORCID
- Venue
- Nature Structural & Molecular Biology
- Published
- 2023-05-11
- Volume
- 30
- Issue
- 6
- Pages
- 770-777
- ISSN
- 1545-9985 (ISSN-L)
- 1545-9993
- PMC
- PMC10279528
- OpenAlex
- W4376134764
- Cited by
- 43
- References
- 6
- Citations by year
- 2026: 9 · 2025: 13 · 2024: 12 · 2023: 8 · 2022: 1
- FWCI
- 6.08
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Nature Structural & Molecular Biology (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- KOPS (University of Konstanz) (submittedVersion, cc-by)
- Repository for Publications and Research Data (ETH Zurich) (submittedVersion, cc-by)
- ETH Zürich Research Collection
- Funders
- National Science Foundation
- University of Virginia
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (212308, 141735, 205601, 163478, 310030)
- Eidgenössische Technische Hochschule Zürich
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Endoplasmic Reticulum Stress and Disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Keywords
- TRAP complex, endoplasmic reticulum, Sec61 translocon, protein translocation, nascent polypeptide chains, insulin secretion, endoplasmic reticulum stress, Caenorhabditis elegans, protein secretion, membrane protein biogenesis
- MeSH terms
- SEC Translocation Channels, Animals, Calcium-Binding Proteins, Endoplasmic Reticulum, Mammals, Membrane Glycoproteins, Membrane Proteins, Receptors, Peptide, Receptors, Cytoplasmic and Nuclear, Protein Transport
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