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ATP synthase hexamer assemblies shape cristae of Toxoplasma mitochondria
by
Ovciarikova, Jana
, Lacombe, Alice
, Sheiner, Lilach
, Kock Flygaard, Rasmus
, Amunts, Alexey
, Fernandes, Paula
, Mühleip, Alexander
in
631/181/735
/ 631/535/1258/1259
/ 631/535/1258/1260
/ 631/80/642/333
/ Apicomplexa
/ ATP synthase
/ ATPase Inhibitory Protein
/ Binding Sites
/ Cardiolipins - chemistry
/ Cardiolipins - metabolism
/ Cristae
/ Cryoelectron Microscopy
/ Dimers
/ Functional analysis
/ Gene Expression
/ Hexamers
/ Humanities and Social Sciences
/ Macromolecules
/ Maintenance
/ Malaria
/ Membranes
/ Mitochondria
/ Mitochondria - genetics
/ Mitochondria - metabolism
/ Mitochondria - ultrastructure
/ Mitochondrial Membranes - metabolism
/ Mitochondrial Membranes - ultrastructure
/ Mitochondrial Proton-Translocating ATPases - chemistry
/ Mitochondrial Proton-Translocating ATPases - genetics
/ Mitochondrial Proton-Translocating ATPases - metabolism
/ Models, Molecular
/ Morphology
/ multidisciplinary
/ Parasites
/ Protein Binding
/ Protein Conformation, alpha-Helical
/ Protein Conformation, beta-Strand
/ Protein Interaction Domains and Motifs
/ Protein Multimerization
/ Protein Subunits - chemistry
/ Protein Subunits - genetics
/ Protein Subunits - metabolism
/ Proteins - chemistry
/ Proteins - genetics
/ Proteins - metabolism
/ Protozoan Proteins - chemistry
/ Protozoan Proteins - genetics
/ Protozoan Proteins - metabolism
/ Pyramids
/ Science
/ Science (multidisciplinary)
/ Structure-function relationships
/ Substrate Specificity
/ Thermodynamics
/ Toxoplasma - genetics
/ Toxoplasma - metabolism
/ Toxoplasma - ultrastructure
/ Toxoplasmosis
/ Vector-borne diseases
2021
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ATP synthase hexamer assemblies shape cristae of Toxoplasma mitochondria
by
Ovciarikova, Jana
, Lacombe, Alice
, Sheiner, Lilach
, Kock Flygaard, Rasmus
, Amunts, Alexey
, Fernandes, Paula
, Mühleip, Alexander
in
631/181/735
/ 631/535/1258/1259
/ 631/535/1258/1260
/ 631/80/642/333
/ Apicomplexa
/ ATP synthase
/ ATPase Inhibitory Protein
/ Binding Sites
/ Cardiolipins - chemistry
/ Cardiolipins - metabolism
/ Cristae
/ Cryoelectron Microscopy
/ Dimers
/ Functional analysis
/ Gene Expression
/ Hexamers
/ Humanities and Social Sciences
/ Macromolecules
/ Maintenance
/ Malaria
/ Membranes
/ Mitochondria
/ Mitochondria - genetics
/ Mitochondria - metabolism
/ Mitochondria - ultrastructure
/ Mitochondrial Membranes - metabolism
/ Mitochondrial Membranes - ultrastructure
/ Mitochondrial Proton-Translocating ATPases - chemistry
/ Mitochondrial Proton-Translocating ATPases - genetics
/ Mitochondrial Proton-Translocating ATPases - metabolism
/ Models, Molecular
/ Morphology
/ multidisciplinary
/ Parasites
/ Protein Binding
/ Protein Conformation, alpha-Helical
/ Protein Conformation, beta-Strand
/ Protein Interaction Domains and Motifs
/ Protein Multimerization
/ Protein Subunits - chemistry
/ Protein Subunits - genetics
/ Protein Subunits - metabolism
/ Proteins - chemistry
/ Proteins - genetics
/ Proteins - metabolism
/ Protozoan Proteins - chemistry
/ Protozoan Proteins - genetics
/ Protozoan Proteins - metabolism
/ Pyramids
/ Science
/ Science (multidisciplinary)
/ Structure-function relationships
/ Substrate Specificity
/ Thermodynamics
/ Toxoplasma - genetics
/ Toxoplasma - metabolism
/ Toxoplasma - ultrastructure
/ Toxoplasmosis
/ Vector-borne diseases
2021
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ATP synthase hexamer assemblies shape cristae of Toxoplasma mitochondria
by
Ovciarikova, Jana
, Lacombe, Alice
, Sheiner, Lilach
, Kock Flygaard, Rasmus
, Amunts, Alexey
, Fernandes, Paula
, Mühleip, Alexander
in
631/181/735
/ 631/535/1258/1259
/ 631/535/1258/1260
/ 631/80/642/333
/ Apicomplexa
/ ATP synthase
/ ATPase Inhibitory Protein
/ Binding Sites
/ Cardiolipins - chemistry
/ Cardiolipins - metabolism
/ Cristae
/ Cryoelectron Microscopy
/ Dimers
/ Functional analysis
/ Gene Expression
/ Hexamers
/ Humanities and Social Sciences
/ Macromolecules
/ Maintenance
/ Malaria
/ Membranes
/ Mitochondria
/ Mitochondria - genetics
/ Mitochondria - metabolism
/ Mitochondria - ultrastructure
/ Mitochondrial Membranes - metabolism
/ Mitochondrial Membranes - ultrastructure
/ Mitochondrial Proton-Translocating ATPases - chemistry
/ Mitochondrial Proton-Translocating ATPases - genetics
/ Mitochondrial Proton-Translocating ATPases - metabolism
/ Models, Molecular
/ Morphology
/ multidisciplinary
/ Parasites
/ Protein Binding
/ Protein Conformation, alpha-Helical
/ Protein Conformation, beta-Strand
/ Protein Interaction Domains and Motifs
/ Protein Multimerization
/ Protein Subunits - chemistry
/ Protein Subunits - genetics
/ Protein Subunits - metabolism
/ Proteins - chemistry
/ Proteins - genetics
/ Proteins - metabolism
/ Protozoan Proteins - chemistry
/ Protozoan Proteins - genetics
/ Protozoan Proteins - metabolism
/ Pyramids
/ Science
/ Science (multidisciplinary)
/ Structure-function relationships
/ Substrate Specificity
/ Thermodynamics
/ Toxoplasma - genetics
/ Toxoplasma - metabolism
/ Toxoplasma - ultrastructure
/ Toxoplasmosis
/ Vector-borne diseases
2021
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ATP synthase hexamer assemblies shape cristae of Toxoplasma mitochondria
Journal Article
ATP synthase hexamer assemblies shape cristae of Toxoplasma mitochondria
2021
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Overview
Mitochondrial ATP synthase plays a key role in inducing membrane curvature to establish cristae. In Apicomplexa causing diseases such as malaria and toxoplasmosis, an unusual cristae morphology has been observed, but its structural basis is unknown. Here, we report that the apicomplexan ATP synthase assembles into cyclic hexamers, essential to shape their distinct cristae. Cryo-EM was used to determine the structure of the hexamer, which is held together by interactions between parasite-specific subunits in the lumenal region. Overall, we identified 17 apicomplexan-specific subunits, and a minimal and nuclear-encoded subunit
-a
. The hexamer consists of three dimers with an extensive dimer interface that includes bound cardiolipins and the inhibitor IF
1
. Cryo-ET and subtomogram averaging revealed that hexamers arrange into ~20-megadalton pentagonal pyramids in the curved apical membrane regions. Knockout of the linker protein ATPTG11 resulted in the loss of pentagonal pyramids with concomitant aberrantly shaped cristae. Together, this demonstrates that the unique macromolecular arrangement is critical for the maintenance of cristae morphology in Apicomplexa.
Structural and functional analysis of mitochondria from the human parasite
Toxoplasma gondii
reveals that its ATP synthase assembles into cyclic hexamers, arranged together in a form of pentagonal pyramids required for maintenance of cristae morphology in Apicomplexa.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ Cristae
/ Dimers
/ Hexamers
/ Humanities and Social Sciences
/ Malaria
/ Mitochondria - ultrastructure
/ Mitochondrial Membranes - metabolism
/ Mitochondrial Membranes - ultrastructure
/ Mitochondrial Proton-Translocating ATPases - chemistry
/ Mitochondrial Proton-Translocating ATPases - genetics
/ Mitochondrial Proton-Translocating ATPases - metabolism
/ Protein Conformation, alpha-Helical
/ Protein Conformation, beta-Strand
/ Protein Interaction Domains and Motifs
/ Protein Subunits - chemistry
/ Protein Subunits - metabolism
/ Protozoan Proteins - chemistry
/ Protozoan Proteins - genetics
/ Protozoan Proteins - metabolism
/ Pyramids
/ Science
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