PXD031140

PXD031140 is an original dataset announced via ProteomeXchange.

Title	Intramembrane client recognition potentiates the chaperone functions of calnexin
Description	One-third of the human proteome is comprised of membrane proteins, which are particularly vulnerable to misfolding and often require folding assistance by molecular chaperones. Calnexin (CNX), which engages client proteins via its sugar-binding lectin domain, is one of the most abundant ER chaperones, and plays an important role in membrane protein biogenesis. Based on mass spectrometric analyses, we here show that calnexin interacts with a large number of nonglycosylated membrane proteins, indicative of additional nonlectin binding modes. We find that calnexin preferentially bind misfolded membrane proteins and that it uses its single transmembrane domain (TMD) for client recognition. Combining experimental and computational approaches, we systematically dissect signatures for intramembrane client recognition by calnexin, and identify sequence motifs within the calnexin TMD region that mediate client binding. Building on this, we show that intramembrane client binding potentiates the chaperone functions of calnexin. Together, these data reveal a widespread role of calnexin client recognition in the lipid bilayer, which synergizes with its established lectin-based substrate binding. Molecular chaperones thus can combine different interaction modes to support the biogenesis of the diverse eukaryotic membrane proteome.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:32:06.955.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Nina Bach
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	methionine oxidation with neutral loss of 64 Da; mono N-acetylated residue; iodoacetamide derivatized residue
Instrument	timsTOF Pro; Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2022-01-21 07:34:50	ID requested
1	2022-11-09 06:16:52	announced
⏵ 2	2023-11-14 08:32:09	announced	2023-11-14: Updated project metadata.

Bloemeke N, Meighen-Berger K, Hitzenberger M, Bach NC, Parr M, Coelho JP, Frishman D, Zacharias M, Sieber SA, Feige MJ, Intramembrane client recognition potentiates the chaperone functions of calnexin. EMBO J, 41(24):e110959(2022) [pubmed]

submitter keyword: membrane proteins, protein quality control, molecular chaperones, Calnexin

Matthias J. Feige
contact affiliation	Technical University of Munich Department of Chemistry and Institute for Advanced Study Lichtenbergstr. 4 85748 Garching, Germany
contact email	matthias.feige@tum.de
lab head
Nina Bach
contact affiliation	TU München
contact email	nina.bach@tum.de
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2022/11/PXD031140

PRIDE project URI

• PRIDE
  1. PXD031140
     1. Label: PRIDE project
     2. Name: Intramembrane client recognition potentiates the chaperone functions of calnexin