9bpg

From Proteopedia

Artemia franciscana ATP synthase FO domain, state 1, pH 7.0

Structural highlights

9bpg is a 10 chain structure with sequence from Artemia franciscana. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 3.3Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

ATP6_ARTSF Mitochondrial membrane ATP synthase (F(1)F(0) ATP synthase or Complex V) produces ATP from ADP in the presence of a proton gradient across the membrane which is generated by electron transport complexes of the respiratory chain. F-type ATPases consist of two structural domains, F(1) - containing the extramembraneous catalytic core and F(0) - containing the membrane proton channel, linked together by a central stalk and a peripheral stalk. During catalysis, ATP synthesis in the catalytic domain of F(1) is coupled via a rotary mechanism of the central stalk subunits to proton translocation. Key component of the proton channel; it may play a direct role in the translocation of protons across the membrane.

Publication Abstract from PubMed

Mammalian mitochondria undergo Ca(2+)-induced and cyclosporinA (CsA)-regulated permeability transition (mPT) by activating the mitochondrial permeability transition pore (mPTP) situated in mitochondrial inner membranes. Ca(2+)-induced prolonged openings of mPTP under certain pathological conditions result in mitochondrial swelling and rupture of the outer membrane, leading to mitochondrial dysfunction and cell death. While the exact molecular composition and structure of mPTP remain unknown, mammalian ATP synthase was reported to form voltage and Ca(2+)-activated leak channels involved in mPT. Unlike in mammals, mitochondria of the crustacean Artemia franciscana have the ability to accumulate large amounts of Ca(2+) without undergoing the mPT. Here, we performed structural and functional analysis of A. franciscana ATP synthase to study the molecular mechanism of mPTP inhibition in this organism. We found that the channel formed by the A. franciscana ATP synthase dwells predominantly in its inactive state and is insensitive to Ca(2+), in contrast to porcine heart ATP synthase. Single-particle cryo-electron microscopy (cryo-EM) analysis revealed distinct structural features in A. franciscana ATP synthase compared with mammals. The stronger density of the e-subunit C-terminal region and its enhanced interaction with the c-ring were found in A. franciscana ATP synthase. These data suggest an inactivation mechanism of the ATP synthase leak channel and its possible contribution to the lack of mPT in this organism.

Cryo-EM structure of the brine shrimp mitochondrial ATP synthase suggests an inactivation mechanism for the ATP synthase leak channel.,Kumar A, da Fonseca Rezende E Mello J, Wu Y, Morris D, Mezghani I, Smith E, Rombauts S, Bossier P, Krahn J, Sigworth FJ, Mnatsakanyan N Cell Death Differ. 2025 Mar 19. doi: 10.1038/s41418-025-01476-w. PMID:40108410^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Kumar A, da Fonseca Rezende E Mello J, Wu Y, Morris D, Mezghani I, Smith E, Rombauts S, Bossier P, Krahn J, Sigworth FJ, Mnatsakanyan N. Cryo-EM structure of the brine shrimp mitochondrial ATP synthase suggests an inactivation mechanism for the ATP synthase leak channel. Cell Death Differ. 2025 Mar 19. PMID:40108410 doi:10.1038/s41418-025-01476-w