9IHO

Open state without NUQM and without flavoprotein (classification state 4) of Pichia pastoris mitochondrial complex I in cMSP26 nanodiscs

Summary for 9IHO

• Entry DOI: 10.2210/pdb9iho/pdb
• EMDB information: 52875
• Descriptor: NADH-ubiquinone oxidoreductase chain 3, NADH-ubiquinone oxidoreductase chain 5, NADH-ubiquinone oxidoreductase chain 4, ... (49 entities in total)
• Functional Keywords: nadh:ubiquinone oxidoreductase nanodisc membrane protein complex, membrane protein
• Biological source: Komagataella pastoris; More
• Total number of polymer chains: 41
• Total formula weight: 980151.69

Authors

Grba, D.N.,Hirst, J. (deposition date: 2025-02-21, release date: 2025-10-15)

Primary citation

Lee, C.S.,Grba, D.N.,Wright, J.J.,Ivanov, B.S.,Hirst, J.
Global conformations of Pichia pastoris complex I are distinguished by the binding of a unique interdomain bridging subunit.
Sci Adv, 11:eadz0693-eadz0693, 2025

PubMed Abstract: Complex I (CI; NADH ubiquinone oxidoreductase) is central to energy generation and metabolic homeostasis in mammalian cells but contributes to adverse outcome pathways under challenging conditions. During ischemia, mammalian CI transitions from a turnover-ready, structurally "closed" state toward a dormant "open" state that prevents it from functioning in reverse during reperfusion to produce reactive oxygen species. Unfortunately, simpler, genetically tractable CI models do not recapitulate the same regulatory behavior, compromising mechanistic studies. Here, we report the structure of isolated CI from the yeast (-CI) and identify distinct closed and open states that resemble those of mammalian CI. Notably, a hitherto-unknown protein (NUQM) completes an interdomain bridge in only the closed state, implying that NUQM stabilizes it by restricting the conformational changes of opening. The direct correlation of NUQM binding with closed/open status in -CI provides opportunities for investigating regulatory mechanisms relevant to reversible catalysis and ischemia-reperfusion injury.

PubMed: 41032597
DOI: 10.1126/sciadv.adz0693

Experimental method

ELECTRON MICROSCOPY (3.8 Å)