PXD031792

PXD031792 is an original dataset announced via ProteomeXchange.

Title	1 Structure of the peroxisomal retro-translocon formed by a heterotrimeric ubiquitin ligase 2 complex
Description	Peroxisomes are ubiquitous organelles that house various metabolic reactions and are essential for human health. Luminal peroxisomal proteins are imported from the cytosol by mobile receptors, which then recycle back to the cytosol by a poorly understood process. Recycling requires receptor modification by a membrane-embedded ubiquitin ligase complex comprised of three RING finger (RF) domain-containing proteins (Pex2, Pex10, and Pex12). Here, we report a cryo-electron microscopy (cryo-EM) structure of the ligase complex, which together with biochemical and in vivo experiments reveals its function as a retro-translocon for peroxisomal import receptors. Each subunit of the complex contributes five transmembrane segments that co-assemble into an open channel. The three RFs form a cytosolic tower, with RF2 positioned above the channel pore. We propose that the N-terminus of a recycling receptor is inserted from the peroxisomal lumen into the pore and modified by RF2 to enable extraction into the cytosol. If recycling is compromised, receptors are polyubiquitinated by the concerted action of RF10 and RF12 and degraded. This polyubiquitination pathway also maintains the homeostasis of other peroxisomal import factors. Our results clarify a crucial step during peroxisomal protein import and reveal why mutations in the ligase complex cause human disease.
HostingRepository	PRIDE
AnnounceDate	2022-07-20
AnnouncementXML	Submission_2022-07-20_05:19:12.378.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Joao Paulo
SpeciesList	scientific name: Saccharomyces cerevisiae (Baker's yeast); NCBI TaxID: 4932;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2022-02-21 03:37:09	ID requested
⏵ 1	2022-07-20 05:19:13	announced

Feng P, Wu X, Erramilli SK, Paulo JA, Knejski P, Gygi SP, Kossiakoff AA, Rapoport TA, A peroxisomal ubiquitin ligase complex forms a retrotranslocation channel. Nature, 607(7918):374-380(2022) [pubmed]

submitter keyword: Peroxisomes, cryo-EM, polyubiquitination, yeast, TMTpro

Tom Rapoport
contact affiliation	Department of Cell Biology Harvard Medical School Boston, MA, USA
contact email	tom_rapoport@hms.harvard.edu
lab head
Joao Paulo
contact affiliation	Harvard Medical School
contact email	joao_paulo@post.harvard.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD031792
     1. Label: PRIDE project
     2. Name: 1 Structure of the peroxisomal retro-translocon formed by a heterotrimeric ubiquitin ligase 2 complex