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Recognition of transmembrane helices by the endoplasmic reticulum translocon
Open accessAbstract
Membrane proteins depend on complex translocation machineries for insertion into target membranes. Although it has long been known that an abundance of nonpolar residues in transmembrane helices is the principal criterion for membrane insertion, the specific sequence-coding for transmembrane helices has not been identified. By challenging the endoplasmic reticulum Sec61 translocon with an extensive set of designed polypeptide segments, we have determined the basic features of this code, including a ‘biological’ hydrophobicity scale. We find that membrane insertion depends strongly on the position of polar residues within transmembrane segments, adding a new dimension to the problem of predicting transmembrane helices from amino acid sequences. Our results indicate that direct protein–lipid interactions are critical during translocon-mediated membrane insertion.
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Citations
Cited by
Protein translocation across the eukaryotic endoplasmic reticulum and bacterial plasma membranes.
Rapoport, T. A. (2007) · Nature · doi:10.1038/nature06384 · Cited by 977
Molecular code for transmembrane-helix recognition by the Sec61 translocon.
Hessa, T., Meindl-Beinker, N. M., Bernsel, A., Kim, H., Sato, Y., Lerch-Bader, M., Nilsson, I., White, S. H., & von Heijne, G. (2007) · Nature · doi:10.1038/nature06387 · Cited by 708
Self-citationvon Heijne, G. (2006) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2063 · Cited by 538
Self-citationViklund, H., & Elofsson, A. (2008) · Bioinformatics · doi:10.1093/bioinformatics/btn221 · Cited by 382
Five computational developability guidelines for therapeutic antibody profiling
Raybould, M. I. J., Marks, C., Krawczyk, K., Taddese, B., Nowak, J., Lewis, A. P., Bujotzek, A., Shi, J., & Deane, C. M. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1810576116 · Cited by 357
Metadata
- Authors
- Hessa, T., Kim, H., Bihlmaier, K., Lundin, C., Boekel, J., Andersson, H., Nilsson, I., White, S. H., & von Heijne, G.
- Venue
- Nature
- Published
- 2005-01
- Volume
- 433
- Issue
- 7024
- Pages
- 377-381
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2025859600
- Cited by
- 996
- References
- 0
- FWCI
- 26.74
- Type
- journal article
- Language
- en
- Open access
- green
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- Hessa, T., Kim, H., Bihlmaier, K., Lundin, C., Boekel, J., Andersson, H., Nilsson, I., White, S. H., & von Heijne, G. (2005). Recognition of transmembrane helices by the endoplasmic reticulum translocon. Nature. https://doi.org/10.1038/nature03216
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