8h9l
Human ATP synthase F1 domain, state 3a
Structural highlights
DiseaseATPA_HUMAN Isolated ATP synthase deficiency. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry. FunctionATPA_HUMAN 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. Subunits alpha and beta form the catalytic core in F(1). Rotation of the central stalk against the surrounding alpha(3)beta(3) subunits leads to hydrolysis of ATP in three separate catalytic sites on the beta subunits. Subunit alpha does not bear the catalytic high-affinity ATP-binding sites (By similarity). Binds the bacterial siderophore enterobactin and can promote mitochondrial accumulation of enterobactin-derived iron ions (PubMed:30146159).[UniProtKB:P19483][1] Publication Abstract from PubMedBiological energy currency ATP is produced by F(1)F(o)-ATP synthase. However, the molecular mechanism for human ATP synthase action remains unknown. Here, we present snapshot images for three main rotational states and one substate of human ATP synthase using cryoelectron microscopy. These structures reveal that the release of ADP occurs when the beta subunit of F(1)F(o)-ATP synthase is in the open conformation, showing how ADP binding is coordinated during synthesis. The accommodation of the symmetry mismatch between F(1) and F(o) motors is resolved by the torsional flexing of the entire complex, especially the gamma subunit, and the rotational substep of the c subunit. Water molecules are identified in the inlet and outlet half-channels, suggesting that the proton transfer in these two half-channels proceed via a Grotthus mechanism. Clinically relevant mutations are mapped to the structure, showing that they are mainly located at the subunit-subunit interfaces, thus causing instability of the complex. Structure of the human ATP synthase.,Lai Y, Zhang Y, Zhou S, Xu J, Du Z, Feng Z, Yu L, Zhao Z, Wang W, Tang Y, Yang X, Guddat LW, Liu F, Gao Y, Rao Z, Gong H Mol Cell. 2023 Jun 15;83(12):2137-2147.e4. doi: 10.1016/j.molcel.2023.04.029. , Epub 2023 May 26. PMID:37244256[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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