PXD006849-1

PXD006849 is an original dataset announced via ProteomeXchange.

Title	ZMYND10 functions in a chaperone-relay during axonemal dynein assembly
Description	Molecular chaperones are abundant cellular proteins that promote the folding, function and macromolecular assembly of a diverse set of substrate proteins, also known as clients. Regulation of chaperone specificity and function involves association with a growing set of distinct cofactors, or cochaperones. How these client, co-chaperone and chaperone interactions in vivo underpin the proteostasis network during development and disease remains unclear. We have combined mouse genetics, imaging and quantitative proteomics to systematically characterize a chaperone-cochaperone-client interaction network in mammalian motile ciliated cells. We uncover ZMYND10 to act as a specificity factor for the immunophilin cochaperone FKBP8 and HSP90 chaperone for the biosynthesis of the heavy chains of axonemal dyneins required for cilial beat. We establish a series of protein-protein interactions during cytoplasmic pre-assembly of macromolecular dynein motors, some of which are directly ZMYND10-dependent. In the absence of ZMYND10, failure of these interactions results in misfolded and unstable dynein heavy chains, which together with non-functional folding intermediates, are targeted for degradation. We propose that the motile ciliopathy Primary Ciliary Dyskinesia (PCD), such as seen in Zmynd10 mutants, be reconsidered as a disorder of protein folding, which opens new avenues for development of therapeutics.
HostingRepository	PRIDE
AnnounceDate	2018-07-12
AnnouncementXML	Submission_2018-07-12_06:36:53.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Alex von kriegsheim
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2017-06-30 05:27:32	ID requested
⏵ 1	2018-07-12 06:36:54	announced
2	2024-10-22 04:38:51	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

curator keyword: Biological

submitter keyword: Primary Ciliary Dyskinesia

Alex von Kriegsheim
contact affiliation	University of Edinburgh
contact email	alex.vonkriegsheim@igmm.ed.ac.uk
lab head
Alex von kriegsheim
contact affiliation	Systems Biology
contact email	alex.vonkriegsheim@ucd.ie
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD006849
     1. Label: PRIDE project
     2. Name: ZMYND10 functions in a chaperone-relay during axonemal dynein assembly