PXD062263

PXD062263 is an original dataset announced via ProteomeXchange.

Title	Mechanistic Insights into Metabolon Formation and Substrate Channeling in Coenzyme Q Biosynthesis
Description	Metabolons - transient assemblies of sequential metabolic enzymes - facilitate the reactions of multi-step metabolic pathways. They represent crucial metabolic fineries, yet, how they mechanistically bolster metabolic flux remains enigmatic. Here, we investigate the molecular determinants of metabolon formation and substrate channeling using coarse-grained molecular dynamics simulations and biophysical approaches to coenzyme Q biosynthesis. The COQ metabolon is fastenedsecured by predominantly weak protein-protein interactions and wherein the COQ6-COQ3 enzyme pair is a critical structural hub for metabolon genesis. Selectively disrupting protein-protein associations demonstrates that protein-proximity is imperative for substrate channeling. Randomly shuffling the interaction network nodes reveals that the specific spatial arrangement of consecutive enzymes has minimal effects on product yield. Rather than specific catalytic activities or fine architectural features, proximity between enzymes in complete clusters is pivotal for metabolic flux. We conclude that the COQ metabolon is evolutionarily optimized to generate complete enzyme clusters without strict requirements for specific spatial arrangements. These findings provide mechanistic insights into how metabolic enzymes are spatially organized to achieve enhance efficient multi-step biosynthesis.
HostingRepository	PRIDE
AnnounceDate	2026-06-08
AnnouncementXML	Submission_2026-06-08_07:35:08.716.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Tereza Kadavá
SpeciesList	scientific name: synthetic construct; NCBI TaxID: NEWT:32630;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2025-03-26 09:23:20	ID requested
⏵ 1	2026-06-08 07:35:09	announced

Dataset with its publication pending

submitter keyword: metabolon, microscale thermophoresis, coenzyme Q, Langevin dynamics simulations, cross-linking and bottom-up mass spectrometry, metabolic flux, protein-protein interactions

Albert J.R. Heck
contact affiliation	Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, University of Utrecht
contact email	a.j.r.heck@uu.nl
lab head
Tereza Kadavá
contact affiliation	Utrecht University, Biomolecular Mass Spectrometry and Proteomics
contact email	t.kadava@uu.nl
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD062263
     1. Label: PRIDE project
     2. Name: Mechanistic Insights into Metabolon Formation and Substrate Channeling in Coenzyme Q Biosynthesis