Proteomics Identifies Substrates and a Novel Component in hSnd2-Dependent ER Protein Targeting

Andrea Tirincsi; Sarah O’Keefe; Duy Nguyen; Mark Sicking; Johanna Dudek; Friedrich Förster; Martin Jung; Drazena Hadzibeganovic; Volkhard Helms; Stephen High; Richard Zimmermann; Sven Lang

doi:10.3390/cells11182925

Proteomics Identifies Substrates and a Novel Component in hSnd2-Dependent ER Protein Targeting

Andrea Tirincsi
, Sarah O’Keefe
, Duy Nguyen
, Mark Sicking
, Johanna Dudek
, Friedrich Förster
, Martin Jung
, Drazena Hadzibeganovic
, Volkhard Helms
, Stephen High
, Richard Zimmermann^*
, Sven Lang

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Importing proteins into the endoplasmic reticulum (ER) is essential for about 30% of the human proteome. It involves the targeting of precursor proteins to the ER and their insertion into or translocation across the ER membrane. Furthermore, it relies on signals in the precursor polypeptides and components, which read the signals and facilitate their targeting to a protein-conducting channel in the ER membrane, the Sec61 complex. Compared to the SRP- and TRC-dependent pathways, little is known about the SRP-independent/SND pathway. Our aim was to identify additional components and characterize the client spectrum of the human SND pathway. The established strategy of combining the depletion of the central hSnd2 component from HeLa cells with proteomic and differential protein abundance analysis was used. The SRP and TRC targeting pathways were analyzed in comparison. TMEM109 was characterized as hSnd3. Unlike SRP but similar to TRC, the SND clients are predominantly membrane proteins with N-terminal, central, or C-terminal targeting signals.

Original language	English
Article number	2925
Journal	Cells
Volume	11
Issue number	18
DOIs	https://doi.org/10.3390/cells11182925
Publication status	Published - 19 Sept 2022

Bibliographical note

Funding Information:
F.F., V.H., S.L. and R.Z. were supported by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation), with grants FO716/4-1 to F.F., HE3875/15-1 to V.H., ZI234/13-1 to R.Z., IRTG1830 and SFB894 to S.L. and R.Z.; S.H. was supported by a Welcome Trust Investigator Award in Science 204957/Z/16/Z. They acknowledge support from the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) and Saarland University within the funding program Open Access Publishing.

Publisher Copyright:
© 2022 by the authors.

Funding

F.F., V.H., S.L. and R.Z. were supported by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation), with grants FO716/4-1 to F.F., HE3875/15-1 to V.H., ZI234/13-1 to R.Z., IRTG1830 and SFB894 to S.L. and R.Z.; S.H. was supported by a Welcome Trust Investigator Award in Science 204957/Z/16/Z. They acknowledge support from the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) and Saarland University within the funding program Open Access Publishing.

Keywords

differential protein abundance analysis
endoplasmic reticulum
guided entry of tail-anchored proteins
membrane proteins
protein targeting
protein translocation
Sec61 complex
signal recognition particle
SRP-independent targeting

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10.3390/cells11182925Licence: CC BY

cells-11-02925-v2Final published version, 6.1 MBLicence: CC BY

Cite this

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title = "Proteomics Identifies Substrates and a Novel Component in hSnd2-Dependent ER Protein Targeting",

abstract = "Importing proteins into the endoplasmic reticulum (ER) is essential for about 30\% of the human proteome. It involves the targeting of precursor proteins to the ER and their insertion into or translocation across the ER membrane. Furthermore, it relies on signals in the precursor polypeptides and components, which read the signals and facilitate their targeting to a protein-conducting channel in the ER membrane, the Sec61 complex. Compared to the SRP- and TRC-dependent pathways, little is known about the SRP-independent/SND pathway. Our aim was to identify additional components and characterize the client spectrum of the human SND pathway. The established strategy of combining the depletion of the central hSnd2 component from HeLa cells with proteomic and differential protein abundance analysis was used. The SRP and TRC targeting pathways were analyzed in comparison. TMEM109 was characterized as hSnd3. Unlike SRP but similar to TRC, the SND clients are predominantly membrane proteins with N-terminal, central, or C-terminal targeting signals.",

keywords = "differential protein abundance analysis, endoplasmic reticulum, guided entry of tail-anchored proteins, membrane proteins, protein targeting, protein translocation, Sec61 complex, signal recognition particle, SRP-independent targeting",

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note = "Funding Information: F.F., V.H., S.L. and R.Z. were supported by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation), with grants FO716/4-1 to F.F., HE3875/15-1 to V.H., ZI234/13-1 to R.Z., IRTG1830 and SFB894 to S.L. and R.Z.; S.H. was supported by a Welcome Trust Investigator Award in Science 204957/Z/16/Z. They acknowledge support from the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) and Saarland University within the funding program Open Access Publishing. Publisher Copyright: {\textcopyright} 2022 by the authors.",

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doi = "10.3390/cells11182925",

language = "English",

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AU - Tirincsi, Andrea

AU - O’Keefe, Sarah

AU - Nguyen, Duy

AU - Sicking, Mark

AU - Dudek, Johanna

AU - Förster, Friedrich

AU - Jung, Martin

AU - Hadzibeganovic, Drazena

AU - Helms, Volkhard

AU - High, Stephen

AU - Zimmermann, Richard

AU - Lang, Sven

N1 - Funding Information: F.F., V.H., S.L. and R.Z. were supported by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation), with grants FO716/4-1 to F.F., HE3875/15-1 to V.H., ZI234/13-1 to R.Z., IRTG1830 and SFB894 to S.L. and R.Z.; S.H. was supported by a Welcome Trust Investigator Award in Science 204957/Z/16/Z. They acknowledge support from the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) and Saarland University within the funding program Open Access Publishing. Publisher Copyright: © 2022 by the authors.

PY - 2022/9/19

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N2 - Importing proteins into the endoplasmic reticulum (ER) is essential for about 30% of the human proteome. It involves the targeting of precursor proteins to the ER and their insertion into or translocation across the ER membrane. Furthermore, it relies on signals in the precursor polypeptides and components, which read the signals and facilitate their targeting to a protein-conducting channel in the ER membrane, the Sec61 complex. Compared to the SRP- and TRC-dependent pathways, little is known about the SRP-independent/SND pathway. Our aim was to identify additional components and characterize the client spectrum of the human SND pathway. The established strategy of combining the depletion of the central hSnd2 component from HeLa cells with proteomic and differential protein abundance analysis was used. The SRP and TRC targeting pathways were analyzed in comparison. TMEM109 was characterized as hSnd3. Unlike SRP but similar to TRC, the SND clients are predominantly membrane proteins with N-terminal, central, or C-terminal targeting signals.

AB - Importing proteins into the endoplasmic reticulum (ER) is essential for about 30% of the human proteome. It involves the targeting of precursor proteins to the ER and their insertion into or translocation across the ER membrane. Furthermore, it relies on signals in the precursor polypeptides and components, which read the signals and facilitate their targeting to a protein-conducting channel in the ER membrane, the Sec61 complex. Compared to the SRP- and TRC-dependent pathways, little is known about the SRP-independent/SND pathway. Our aim was to identify additional components and characterize the client spectrum of the human SND pathway. The established strategy of combining the depletion of the central hSnd2 component from HeLa cells with proteomic and differential protein abundance analysis was used. The SRP and TRC targeting pathways were analyzed in comparison. TMEM109 was characterized as hSnd3. Unlike SRP but similar to TRC, the SND clients are predominantly membrane proteins with N-terminal, central, or C-terminal targeting signals.

KW - differential protein abundance analysis

KW - endoplasmic reticulum

KW - guided entry of tail-anchored proteins

KW - membrane proteins

KW - protein targeting

KW - protein translocation

KW - Sec61 complex

KW - signal recognition particle

KW - SRP-independent targeting

UR - https://www.scopus.com/pages/publications/85138335032

U2 - 10.3390/cells11182925

DO - 10.3390/cells11182925

M3 - Article

C2 - 36139500

AN - SCOPUS:85138335032

SN - 2073-4409

VL - 11

JO - Cells

JF - Cells

IS - 18

M1 - 2925

ER -

Proteomics Identifies Substrates and a Novel Component in hSnd2-Dependent ER Protein Targeting

Abstract

Bibliographical note

Funding

Keywords

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