PXD044351-2

PXD044351 is an original dataset announced via ProteomeXchange.

Title	Human CRB1 and CRB2 form homo- and heteromeric protein complexes in the retina
Description	Crumbs homolog 1 (CRB1) is one of the key genes linked to retinitis pigmentosa and Leber congenital amaurosis, which are characterized by a high clinical heterogeneity. The Crumbs family member CRB2 has a similar protein structure to CRB1, and in zebrafish, Crb2 has been shown to interact through the extracellular domain. Here, we show that CRB1 and CRB2 co-localize in the human retina and human iPSC-derived retinal organoids. In retina-specific pull-downs, CRB1 was enriched in CRB2 samples, supporting a CRB1–CRB2 interaction. Furthermore, novel interactors of the crumbs complex were identified, representing a retina-derived protein interaction network. Using co-immunoprecipitation, we further demonstrate that human canonical CRB1 interacts with CRB1 and CRB2, but not with CRB3, which lacks an extracellular domain. Next, we explored how missense mutations in the extracellular domain affect CRB1–CRB2 interactions. We observed no or a mild loss of CRB1–CRB2 interaction, when interrogating various CRB1 or CRB2 missense mutants in vitro. Taken together, our results show a stable interaction of human canonical CRB2 and CRB1 in the retina.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:34:57.922.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Isabel Felicitas Stehle
SpeciesList	scientific name: Sus scrofa domesticus (domestic pig); NCBI TaxID: 9825; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2023-08-04 04:14:57	ID requested
1	2024-04-02 23:43:57	announced
⏵ 2	2024-10-22 06:34:58	announced	2024-10-22: Updated project metadata.

10.26508/LSA.202302440;

submitter keyword: CRB1, Retinitis pigmentosa, affinity proteomics, CRB1-CRB2 interaction, CRB2, Leber Congenital Amaurosis

Dr. Karsten
contact affiliation	Molecular Biology of Retinal Degenerations Institute for Ophthalmic Research Eberhard-Karls University of Tuebingen
contact email	karsten.boldt@uni-tuebingen.de
lab head
Isabel Felicitas Stehle
contact affiliation	Institute for Ophthalmic Research, Eberhard Karls University Tübingen, Elfriede-Aulhorn-Str. 7, 72076 Tübingen, Germany
contact email	isabel.stehle@uni-tuebingen.de
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/2024/04/PXD044351

PRIDE project URI

• PRIDE
  1. PXD044351
     1. Label: PRIDE project
     2. Name: Human CRB1 and CRB2 form homo- and heteromeric protein complexes in the retina