PXD081202-1

PXD081202 is an original dataset announced via ProteomeXchange.

Title	Sbh1/Sec61-beta is a specific signal peptide receptor within the Sec61 channel
Description	In eukaryotes, protein secretion begins with protein translocation through the universally conserved Sec61 channel into the endoplasmic reticulum (ER). Its -subunit, Sbh1 in yeast, enhances ER import of proteins with specific suboptimal signal peptides by an unknown mechanism. The Sbh1 cytosolic N-terminus consists of an intrinsically disordered, non-conserved region (IDR) that has never been visualized in active channel structures, but is close to the translocating polypeptide in the cytosolic channel vestibule. The Sbh1/Sec61 N-terminal IDR is followed by structured 15 amino acids and its C-terminal transmembrane helix, both of which are conserved. We show here that the proline and adjacent conserved residues at the Sbh1 cytosolic/transmembrane domain interface form a hinge that positions the Sbh1 cytosolic domain across the channel vestibule and orients it with respect to the lateral gate. This orientation is critical for Sbh1-dependent protein insertion into the channel. Sbh1-dependence of Sec61 channel insertion is a function of the signal peptide of the respective secretory protein. By chemical crosslinking of purified cytosolic domains of Sbh1 and its paralog Sbh2 to synthetic signal peptides derived from their respective client proteins, we show that the cytosolic domains of Sbh1 and Sbh2 contain specific signal peptide binding sites. The position of the crosslinked residues suggests that signal peptide binding is mediated by the IDRs. We conclude that Sec61beta homologs directly recognize signal peptides of their substrates and guide them into the Sec61 channel; they thus control entry of specific proteins into the secretory pathway.
HostingRepository	PRIDE
AnnounceDate	2026-09-07
AnnouncementXML	Submission_2026-09-07_08:21:32.238.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Florian Stengel
SpeciesList	scientific name: Saccharomyces cerevisiae (Baker's yeast); NCBI TaxID: NEWT:4932;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Eclipse

Revision	Datetime	Status	ChangeLog Entry
0	2026-07-16 12:34:08	ID requested
⏵ 1	2026-09-07 08:21:32	announced

Dataset with its publication pending

submitter keyword: XL-MS Sbh1 signal peptides Sec61 channel

Florian Stengel
contact affiliation	Biology depeartment, University of Konstanz, Germany
contact email	florian.stengel@uni-konstanz.de
lab head
Florian Stengel
contact affiliation	Universität Konstanz
contact email	florian.stengel@uni-konstanz.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD081202
     1. Label: PRIDE project
     2. Name: Sbh1/Sec61-beta is a specific signal peptide receptor within the Sec61 channel