9ZFV

Mitochondrial MDH and OSCP in the peripheral stalk of ATP synthase in Acanthamoeba castellanii

Summary for 9ZFV

• Entry DOI: 10.2210/pdb9zfv/pdb
• EMDB information: 74155
• Descriptor: malate dehydrogenase, mitochondrial ATP synthase subunit oscp, ACANB14707 (3 entities in total)
• Functional Keywords: complex v, oxphos, oxidoreductase
• Biological source: Acanthamoeba castellanii; More
• Total number of polymer chains: 4
• Total formula weight: 157245.20

Authors

Fry, M.Y.,Luce, B.E.,Stefely, J.A.,Samuelson, J.,Mootha, V.K.,Chao, L.H. (deposition date: 2025-12-02, release date: 2026-10-14)

Primary citation

Fry, M.Y.,Luce, B.E.,Stefely, J.A.,Chen, M.Z.,Deng, F.G.,Issa, T.M.,Calvo, S.E.,Samuelson, J.,Mootha, V.K.,Chao, L.H.
Acanthamoeba ATP synthase structure reveals the TCA cycle is tethered to OXPHOS.
Cell, 189:6307-6324.e7, 2026

PubMed Abstract: Oxidative phosphorylation (OXPHOS) is a key metabolic process that couples redox energy to ATP production. While some core OXPHOS complex subunits are found across all domains of life, many have diverged or expanded across evolution-as seen in the protozoan pathogen Acanthamoeba castellanii. By integrating cryo-electron microscopy of unenriched mitochondrial lysate with mass spectrometry proteomics, we resolved the structures of endogenous mitochondrial ATP synthase (complex V), Hsp60, and respiratory complex III from Acanthamoeba. We capture Acanthamoeba ATP synthase in an IF1-inhibited state and reveal how Acanthamoeba-specific subunits and extensions stabilize the molecular machine, which includes a β subunit extension that interfaces with the peripheral stalk. Additionally, we characterize an active malate dehydrogenase (MDH) dimer structurally integrated within the ATP synthase peripheral stalk, thus revealing a direct protein tether between OXPHOS and the tricarboxylic acid cycle. Together, these findings provide structural insight into lineage-specific adaptations in Acanthamoeba that may tune protozoan metabolism.

PubMed: 42822427
DOI: 10.1016/j.cell.2026.08.057

Experimental method

ELECTRON MICROSCOPY (4.21 Å)