TY - JOUR
T1 - Proteomics Identifies Substrates and a Novel Component in hSnd2-Dependent ER Protein Targeting
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
Y1 - 2022/9/19
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 - http://www.scopus.com/inward/record.url?scp=85138335032&partnerID=8YFLogxK
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 -