9ihr

Closed state with NUQM and with flavoprotein (classification state 1) of Pichia pastoris mitochondrial complex I in cMSP26 nanodiscs

spinqualitylabelsall models 9ihr, resolution 2.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9ihr is a 10 chain structure with sequence from Komagataella pastoris. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 2.8Å Ligands: 2MR, 3PE, ACE, CDL, EHZ, FES, FME, FMN, K, NDP, PLC, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function E1UWD4_PICPA Publication Abstract from PubMed 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 Pichia pastoris (Pp-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 Pp-CI provides opportunities for investigating regulatory mechanisms relevant to reversible catalysis and ischemia-reperfusion injury. Global conformations of Pichia pastoris complex I are distinguished by the binding of a unique interdomain bridging subunit.,Lee CS, Grba DN, Wright JJ, Ivanov BS, Hirst J Sci Adv. 2025 Oct 3;11(40):eadz0693. doi: 10.1126/sciadv.adz0693. Epub 2025 Oct , 1. PMID:41032597 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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