PXD027953-1

PXD027953 is an original dataset announced via ProteomeXchange.

Title	Novel roles for ribosomal histidine methylation revealed by proteomics and large-scale cross-linking mass spectrometry
Description	The methylation of histidine residues is increasingly found to be both prevalent throughout the proteome, and also relevant to human disease. Hpm1p mono-methylates H243 in the ribosomal protein Rpl3 and represents the only histidine methyltransferase in Saccharomyces cerevisiae. Interestingly, the hpm1 deletion strain is highly pleiotropic, with many extra-ribosomal phenotypes including improved growth rates in alternative carbon sources. Here we aimed to understand how methylation of one histidine in one ribosomal protein could result in such diverse phenotypes by combining targeted mass spectrometry, growth assays, quantitative proteomics and cross-linking mass spectrometry. We confirmed the localisation and stoichiometry of the H243 site, found unreported sensitivities of Δhpm1 yeast to non-ribosomal stressors, and identified thirty differentially-abundant proteins upon hpm1 knockout, most with clear links to the coordination of sugar metabolism. We adapted the emerging technique of quantitative large scale cross-linking mass spectrometry for use in budding yeast, which resulted in the identification of 1,267 unique in vivo lysine-lysine pairs. By reproducibly monitoring over 350, we detected changes to membrane protein structure, chromatin compaction, and mitochondrial protein-protein interactions, independently of changes in protein abundance themselves. Taken together, these studies reveal a clear role for Hpm1p in the coordination of sugar metabolism, contextualise the deletion strain’s pleiotropy and illustrate how cross-linking mass spectrometry can generate mechanistic insights into complex cellular processes.
HostingRepository	PRIDE
AnnounceDate	2022-08-12
AnnouncementXML	Submission_2022-08-12_01:06:36.910.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Tara Bartolec
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	2021-08-16 06:01:20	ID requested
⏵ 1	2022-08-12 01:06:37	announced

Bartolec TK, Hamey JJ, Keller A, Chavez JD, Bruce JE, Wilkins MR, Differential Proteome and Interactome Analysis Reveal the Basis of Pleiotropy Associated With the Histidine Methyltransferase Hpm1p. Mol Cell Proteomics, 21(7):100249(2022) [pubmed]

submitter keyword: histidine methylation, yeast, cross-linking, SILAC

Marc R. Wilkins
contact affiliation	Systems Biology Initiative School of Biotechnology and Biomolecular Sciences Faculty of Science, The University of New South Wales Sydney, Australia
contact email	m.wilkins@unsw.edu.au
lab head
Tara Bartolec
contact affiliation	UNSW Sydney
contact email	tarabartolec@live.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD027953
     1. Label: PRIDE project
     2. Name: Novel roles for ribosomal histidine methylation revealed by proteomics and large-scale cross-linking mass spectrometry