PXD009189

PXD009189 is an original dataset announced via ProteomeXchange.

Title	A network of chaperones prevents and detects failures in membrane protein lipid bilayer integration
Description	A fundamental step in membrane protein biogenesis is their integration into the lipid bilayer with a defined topology. Despite this, it remains unclear how cells detect and handle failures in membrane integration. Our data show that single point mutations in the membrane protein connexin 32 (Cx32), which cause Charcot-Marie-Tooth disease, can cause failures in membrane integration. This leads to Cx32 transport defects and its rapid degradation. We found multiple chaperones to detect and remedy this aberrant behavior: the ER membrane complex (EMC) aids in membrane integration of low-hydrophobicity transmembrane segments. If they fail to integrate, these are recognized by the ER lumenal chaperone BiP. Ultimately, the E3 ligase gp78 ubiquitinates Cx32 proteins targeting them for degradation. Thus, cells use a coordinated system of chaperones for the complex task of membrane protein biogenesis, which can be compromised by single point mutations, causing human disease.
HostingRepository	PRIDE
AnnounceDate	2019-01-29
AnnouncementXML	Submission_2019-02-11_04:55:32.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Matthias Stahl
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2018-03-12 12:41:20	ID requested
1	2019-01-29 01:08:14	announced
⏵ 2	2019-02-11 04:55:34	announced	Updated publication reference for PubMed record(s): 30737405.

Coelho JPL, Stahl M, Bloemeke N, Meighen-Berger K, Alvira CP, Zhang ZR, Sieber SA, Feige MJ, A network of chaperones prevents and detects failures in membrane protein lipid bilayer integration. Nat Commun, 10(1):672(2019) [pubmed]

submitter keyword: membrane protein, Connexin, topology, protein folding, protein degradation, protein quality control, endoplasmic reticulum, ER membrane complex, chaperone

Stephan A. Sieber
contact affiliation	Lehrstuhl fuer Organische Chemie II Department Chemie TU Muenchen
contact email	stephan.sieber@tum.de
lab head
Matthias Stahl
contact affiliation	Karolinska Institutet
contact email	matthias.stahl@ki.se
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/2019/01/PXD009189

PRIDE project URI

• PRIDE
  1. PXD009189
     1. Label: PRIDE project
     2. Name: A network of chaperones prevents and detects failures in membrane protein lipid bilayer integration