PXD036896-1

PXD036896 is an original dataset announced via ProteomeXchange.

Title	MRPS36 provides a missing link in the eukaryotic 2-oxoglutarate dehydrogenase complex for recruitment of E3 to the E2 core - Phospoproteomics data
Description	The tricarboxylic acid (TCA) cycle, or Krebs cycle, is the central pathway of energy production in eukaryotic cells and plays a key part in aerobic respiration throughout all kingdoms of life. The enzymes involved in this cycle generate the reducing equivalents NADH and FADH2 by a series of enzymatic reactions, which are utilized by the electron transport chain to produce ATP. One of the key enzymes in this cycle is 2-oxoglutarate dehydrogenase (OGDHC), which generates NADH by oxidative decarboxylation of 2-oxoglutarate to succinyl-CoA. Notably, this enzyme consists of multiple subunits as a megadalton protein complex. Thus far, it was thought that OGDHC consists of solely three catalytically active subunits (E1, E2, E3). However in fungi and animals, the small protein MRPS36 has been proposed as a putative additional component. Based on extensive XL-MS data obtained from measurements in both, mice and bovine heart mitochondria, and from phylogenetic analyses, we provide structural evidence that MRPS36 is an exclusive and crucial member of eukaryotic OGDHC. Comparative genomics analysis and computational structure predictions reveal that in eukaryotic OGDHC, E2o does not contain a peripheral subunit-binding (PSBD) domain. Instead, our data provide compelling evidence that in eukaryotes, MRPS36 evolved as E3 adaptor protein, functionally replacing the PSBD domain. Based on our data we provide a refined structural model of the complete eukaryotic OGDHC assembly containing all its 58 subunits (~ 3.4 MDa). The model provides new insights into the protein-protein interactions within the OGDH complex and highlights putative mechanistic implications.
HostingRepository	PRIDE
AnnounceDate	2023-03-10
AnnouncementXML	Submission_2023-03-10_14:08:20.901.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	JohannesHevler
SpeciesList	scientific name: Bos taurus (Bovine); NCBI TaxID: 9913;
ModificationList	phosphorylated residue; acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2022-09-21 09:23:47	ID requested
⏵ 1	2023-03-10 14:08:21	announced
2	2023-11-14 08:27:40	announced	2023-11-14: Updated project metadata.

Hevler JF, Albanese P, Cabrera-Orefice A, Potter A, Jankevics A, Misic J, Scheltema RA, Brandt U, Arnold S, Heck AJR, MRPS36 provides a structural link in the eukaryotic 2-oxoglutarate dehydrogenase complex. Open Biol, 13(3):220363(2023) [pubmed]

submitter keyword: 2-oxoglutarate dehydrogenase (OGDHC)

MRPS36

Tricarboxylic acid (TCA) cycle

Krebs cycle

heart mitochondria

cross-linking mass spectrometry

complexome profiling

structural biology

Comparative genomics

AlbertHeck
contact affiliation	Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, University of Utrecht, Padualaan 8, 3584 CH Utrecht, The Netherlands
contact email	A.J.R.Heck@uu.nl
lab head
JohannesHevler
contact affiliation	Utrecht University
contact email	j.f.hevler@uu.nl
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/2023/03/PXD036896

PRIDE project URI

• PRIDE
  1. PXD036896
     1. Label: PRIDE project
     2. Name: MRPS36 provides a missing link in the eukaryotic 2-oxoglutarate dehydrogenase complex for recruitment of E3 to the E2 core - Phospoproteomics data