PXD073183-1

PXD073183 is an original dataset announced via ProteomeXchange.

Title	Functional Asymmetry and Essential Structural Roles of PDE6α and PDE6β Subunits in Rod Photoreceptor Integrity
Description	Tetrameric rod phosphodiesterase 6 (PDE6) critically regulates cyclic GMP (cGMP) levels in rod photoreceptors comprised of catalytic core α/β heterodimer and two small inhibitory γ subunits. While the rod PDE6 catalytic core is a heterodimer, the cone isoform is an α'/α' homodimer. This structural difference suggests unique roles for each rod subunit. Due to the lack of heterologous expression systems, we leveraged novel transgenic mouse models to examine the functional contributions of the N-terminal Pt motifs and the individual catalytic subunits in vivo. We generated four independent mouse lines: N-terminal deletions (PDE6αΔ2-48AA and PDE6βΔ2-46AA) and active-site mutations (PDE6αH599A and PDE6βH597A) designed to selectively abolish catalytic activity. Native mass spectrometric analysis of heterozygous mice confirmed that only wild-type enzyme was produced. While homozygous mutations in all lines caused complete photoreceptor degeneration, analysis of heterozygous lines revealed a disproportionately greater impact of PDE6β mutations on protein stability, enzymatic activity, and visual function compared to PDE6α. These findings establish that both active subunits are essential for rod integrity but uncover a significant functional asymmetry within the PDE6αβ heterodimer. Our results demonstrate that the PDE6β subunit plays a more dominant role in maintaining the structural and functional pool of the PDE6 enzyme.
HostingRepository	PRIDE
AnnounceDate	2026-05-25
AnnouncementXML	Submission_2026-05-25_11:30:04.701.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Fangyuan Gao
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos; Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2026-01-16 20:27:15	ID requested
⏵ 1	2026-05-25 11:30:05	announced

10.1073/PNAS.2604088123;

submitter keyword: cGMP,phosphodiesterase 6, outer segment, rod photoreceptor, visual transduction

Krzysztof Palczewski
contact affiliation	1Brunason Center for Translational Vision Research, Department of Ophthalmology and Visual Sciences, Gavin Herbert Eye Institute, University of California, Irvine, Irvine, CA, 92697, USA; 2Department of Physiology and Biophysics, University of California, Irvine, Irvine, CA, 92697, USA; 3Department of Chemistry, University of California, Irvine, Irvine, CA, 92697, USA; Department of Molecular Biology and Biochemistry, University of California, Irvine, Irvine, CA, 92697, USA
contact email	kpalczew@uci.edu
lab head
Fangyuan Gao
contact affiliation	University of California, Irvine
contact email	fangyuag@hs.uci.edu
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/2026/05/PXD073183

PRIDE project URI

• PRIDE
  1. PXD073183
     1. Label: PRIDE project
     2. Name: Functional Asymmetry and Essential Structural Roles of PDE6α and PDE6β Subunits in Rod Photoreceptor Integrity