The Molecular Biodiversity of Protein Targeting and Protein Transport Related to the Endoplasmic Reticulum

Tirincsi, Andrea; Sicking, Mark; Hadzibeganovic, Drazena; Haßdenteufel, Sarah; Lang, Sven

doi:10.3390/ijms23010143

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The Molecular Biodiversity of Protein Targeting and Protein Transport Related to the Endoplasmic Reticulum

by

Andrea Tirincsi

¹,

Mark Sicking

¹,

Drazena Hadzibeganovic

¹,

Sarah Haßdenteufel

^2,* and

Sven Lang

^1,*

¹

Department of Medical Biochemistry and Molecular Biology, Saarland University, 66421 Homburg, Germany

²

Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 7610001, Israel

^*

Authors to whom correspondence should be addressed.

Int. J. Mol. Sci. 2022, 23(1), 143; https://doi.org/10.3390/ijms23010143

Submission received: 27 October 2021 / Revised: 19 December 2021 / Accepted: 20 December 2021 / Published: 23 December 2021

(This article belongs to the Special Issue Mechanisms of ER Protein Import)

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Abstract

Looking at the variety of the thousands of different polypeptides that have been focused on in the research on the endoplasmic reticulum from the last five decades taught us one humble lesson: no one size fits all. Cells use an impressive array of components to enable the safe transport of protein cargo from the cytosolic ribosomes to the endoplasmic reticulum. Safety during the transit is warranted by the interplay of cytosolic chaperones, membrane receptors, and protein translocases that together form functional networks and serve as protein targeting and translocation routes. While two targeting routes to the endoplasmic reticulum, SRP (signal recognition particle) and GET (guided entry of tail-anchored proteins), prefer targeting determinants at the N- and C-terminus of the cargo polypeptide, respectively, the recently discovered SND (SRP-independent) route seems to preferentially cater for cargos with non-generic targeting signals that are less hydrophobic or more distant from the termini. With an emphasis on targeting routes and protein translocases, we will discuss those functional networks that drive efficient protein topogenesis and shed light on their redundant and dynamic nature in health and disease.

Keywords: endoplasmic reticulum; GET; protein targeting; protein transport; SND; SRP; Sec61 complex; EMC; positive-inside rule; hydrophobicity; signal peptide; transmembrane helix

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MDPI and ACS Style

Tirincsi, A.; Sicking, M.; Hadzibeganovic, D.; Haßdenteufel, S.; Lang, S. The Molecular Biodiversity of Protein Targeting and Protein Transport Related to the Endoplasmic Reticulum. Int. J. Mol. Sci. 2022, 23, 143. https://doi.org/10.3390/ijms23010143

AMA Style

Tirincsi A, Sicking M, Hadzibeganovic D, Haßdenteufel S, Lang S. The Molecular Biodiversity of Protein Targeting and Protein Transport Related to the Endoplasmic Reticulum. International Journal of Molecular Sciences. 2022; 23(1):143. https://doi.org/10.3390/ijms23010143

Chicago/Turabian Style

Tirincsi, Andrea, Mark Sicking, Drazena Hadzibeganovic, Sarah Haßdenteufel, and Sven Lang. 2022. "The Molecular Biodiversity of Protein Targeting and Protein Transport Related to the Endoplasmic Reticulum" International Journal of Molecular Sciences 23, no. 1: 143. https://doi.org/10.3390/ijms23010143

APA Style

Tirincsi, A., Sicking, M., Hadzibeganovic, D., Haßdenteufel, S., & Lang, S. (2022). The Molecular Biodiversity of Protein Targeting and Protein Transport Related to the Endoplasmic Reticulum. International Journal of Molecular Sciences, 23(1), 143. https://doi.org/10.3390/ijms23010143

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

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The Molecular Biodiversity of Protein Targeting and Protein Transport Related to the Endoplasmic Reticulum

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