PXD012082

PXD012082 is an original dataset announced via ProteomeXchange.

Title	Regulation of the endosomal SNX27 retromer by OTULIN
Description	OTULIN specifically hydrolyzes methionine1 (Met1)-linked ubiquitin chains conjugated by LUBAC (linear ubiquitin chain assembly complex). Using mass spectrometry, we discovered an interaction of OTULIN with SNX27 (sorting nexin 27), an adaptor of the endosomal retromer complex responsible for protein recycling to the cell surface. The C-terminal PDZ binding motif (PDZbm) in OTULIN associates with the cargo-binding site in the PDZ domain of SNX27. By solving the structure of the OTU domain in complex with the PDZ domain, we demonstrate that a second interface contributes to the selective, high affinity interaction of OTULIN and SNX27. SNX27 does not affect OTULIN catalytic activity, OTULIN-LUBAC binding or Met1-linked ubiquitin chain homeostasis. However, via association OTULIN antagonizes SNX27-dependent cargo loading, binding of SNX27 to the retromer subunit VPS26 and endosome-to-membrane trafficking. Thus, we define an additional, non-catalytic function of OTULIN in the regulation of retromer assembly and protein recycling to the cell surface.
HostingRepository	PRIDE
AnnounceDate	2019-09-25
AnnouncementXML	Submission_2019-09-25_06:03:28.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Adan Pinto-Fernandez
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; deaminated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2018-12-17 06:26:06	ID requested
⏵ 1	2019-09-25 06:03:30	announced

Stangl A, Elliott PR, Pinto-Fernandez A, Bonham S, Harrison L, Schaub A, Kutzner K, Keusekotten K, Pfluger PT, El Oualid F, Kessler BM, Komander D, Krappmann D, Regulation of the endosomal SNX27-retromer by OTULIN. Nat Commun, 10(1):4320(2019) [pubmed]

submitter keyword: OTULIN, acitivity-based probe, interactome

Benedikt Kessler
contact affiliation	TDI-NDM University of Oxford
contact email	benedikt.kessler@ndm.ox.ac.uk
lab head
Adan Pinto-Fernandez
contact affiliation	University of Oxford
contact email	adan.pintofernandez@ndm.ox.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD012082
     1. Label: PRIDE project
     2. Name: Regulation of the endosomal SNX27 retromer by OTULIN