PXD061083

PXD061083 is an original dataset announced via ProteomeXchange.

Title	Mesoscale regulation of microtubule-organising centres by the E3 ligase TRIM37
Description	Centrosomes ensure accurate chromosome segregation during cell division. Although the regulation of centrosome number is well-established, less is known about the suppression of non-centrosomal Microtubule-Organising Centres (ncMTOCs). The E3 ligase TRIM37, implicated in Mulibrey nanism and 17q23-amplified cancers, has emerged as a key regulator of both centrosomes and ncMTOCs. Yet, the mechanism by which TRIM37 achieves enzymatic activation to target these mesoscale structures had thus far remained unknown. Here, we elucidate the activation process of TRIM37, unveiling a process that initiates with TRAF domain-directed substrate recognition, followed by B-box domain-mediated oligomerisation, and culminates in RING domain dimerisation. Using optogenetics, we demonstrate that the E3 activity of TRIM37 is directly coupled to the assembly state of its substrates, being activated only when centrosomal proteins cluster into higher-order assemblies resembling MTOCs. This regulatory framework provides a mechanistic basis for understanding TRIM37-driven pathologies and echoes the restriction of the HIV capsid by TRIM5, thus unveiling a conserved activation blueprint among TRIM proteins to control turnover of complexes assembled at the mesoscale level.
HostingRepository	PRIDE
AnnounceDate	2025-03-18
AnnouncementXML	Submission_2025-03-18_10:55:11.531.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Zhong YI Yeow
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	biotinylated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2025-02-22 11:38:06	ID requested
⏵ 1	2025-03-18 10:55:11	announced

Dataset with its publication pending

submitter keyword: E3 ubiquitin ligases, centrosomes and MTOCs, 17q23-amplified cancers,TRIM37, Mulibrey Nanism disorder, TRIM proteins, mesoscale protein assembly

Andrew J Holland
contact affiliation	Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
contact email	aholland@jhmi.edu
lab head
Zhong YI Yeow
contact affiliation	Johns Hopkins School of Medicine
contact email	zyeow1@jh.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD061083
     1. Label: PRIDE project
     2. Name: Mesoscale regulation of microtubule-organising centres by the E3 ligase TRIM37