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Structure paper

TitleStructural basis of respiratory complex adaptation to cold temperatures.
Journal, issue, pagesCell, Year 2024
Publish dateOct 3, 2024
AuthorsYoung-Cheul Shin / Pedro Latorre-Muro / Amina Djurabekova / Oleksii Zdorevskyi / Christopher F Bennett / Nils Burger / Kangkang Song / Chen Xu / Joao A Paulo / Steven P Gygi / Vivek Sharma / Maofu Liao / Pere Puigserver /
PubMed AbstractIn response to cold, mammals activate brown fat for respiratory-dependent thermogenesis reliant on the electron transport chain. Yet, the structural basis of respiratory complex adaptation upon cold ...In response to cold, mammals activate brown fat for respiratory-dependent thermogenesis reliant on the electron transport chain. Yet, the structural basis of respiratory complex adaptation upon cold exposure remains elusive. Herein, we combined thermoregulatory physiology and cryoelectron microscopy (cryo-EM) to study endogenous respiratory supercomplexes from mice exposed to different temperatures. A cold-induced conformation of CI:III (termed type 2) supercomplex was identified with a ∼25° rotation of CIII around its inter-dimer axis, shortening inter-complex Q exchange space, and exhibiting catalytic states that favor electron transfer. Large-scale supercomplex simulations in mitochondrial membranes reveal how lipid-protein arrangements stabilize type 2 complexes to enhance catalytic activity. Together, our cryo-EM studies, multiscale simulations, and biochemical analyses unveil the thermoregulatory mechanisms and dynamics of increased respiratory capacity in brown fat at the structural and energetic level.
External linksCell / PubMed:39395414
MethodsEM (single particle)
Resolution3.1 - 6.3 Å
Structure data

EMDB-35313, PDB-8iao:
Respiratory complex CI:CIII2, type I, Wild type mouse under thermoneutral temperature
Method: EM (single particle) / Resolution: 4.2 Å

EMDB-35314, PDB-8iap:
Respiratory complex Peripheral Arm of CI, focus-refined map of type I, Wild type mouse under thermoneutral temperature
Method: EM (single particle) / Resolution: 3.2 Å

EMDB-35315, PDB-8iaq:
Respiratory complex Membrane domain of CI, focused map of type I, Wild type mouse under thermoneutral temperature
Method: EM (single particle) / Resolution: 3.4 Å

EMDB-35316, PDB-8iar:
Respiratory complex CIII2, focus-refined of type I, Wild type mouse under thermoneutral temperature
Method: EM (single particle) / Resolution: 3.4 Å

EMDB-35331, PDB-8ib4:
Respiratory complex CI:CIII2, type IA, Wild type mouse under cold temperature
Method: EM (single particle) / Resolution: 4.3 Å

EMDB-35332, PDB-8ib5:
Respiratory complex Peripheral Arm of CI, focus-refined map of type IA, Wild type mouse under cold temperature
Method: EM (single particle) / Resolution: 3.3 Å

EMDB-35333, PDB-8ib6:
Respiratory complex Membrane domain of CI, focus-refined of type IA, Wild type mouse under cold temperature
Method: EM (single particle) / Resolution: 3.3 Å

EMDB-35334, PDB-8ib7:
Respiratory complex CIII2, focus-refined of type IA, Wild type mouse under cold temperature
Method: EM (single particle) / Resolution: 3.4 Å

EMDB-35336, PDB-8ib9:
Respiratory complex CI:CIII2, type IB, Wild type mouse under cold temperature
Method: EM (single particle) / Resolution: 4.3 Å

EMDB-35337, PDB-8iba:
Respiratory complex Peripheral Arm of CI, focus-refined map of type IB, Wild type mouse under cold temperature
Method: EM (single particle) / Resolution: 3.2 Å

EMDB-35338, PDB-8ibb:
Respiratory complex Membrane domain of CI, focus-refined of type IB, Wild type mouse under cold temperature
Method: EM (single particle) / Resolution: 3.3 Å

EMDB-35339, PDB-8ibc:
Respiratory complex CIII2, focus-refined of type IB, Wild type mouse under cold temperature
Method: EM (single particle) / Resolution: 3.6 Å

EMDB-35340, PDB-8ibd:
Respiratory complex CI:CIII2, type II, Wild type mouse under cold temperature
Method: EM (single particle) / Resolution: 4.2 Å

EMDB-35341, PDB-8ibe:
Respiratory complex Peripheral Arm of CI, focus-refined map of type II, Wild type mouse under cold temperature
Method: EM (single particle) / Resolution: 3.3 Å

EMDB-35342, PDB-8ibf:
Respiratory complex Membrane domain of CI, focus-refined of type II, Wild type mouse under cold temperature
Method: EM (single particle) / Resolution: 3.3 Å

EMDB-35343, PDB-8ibg:
Respiratory complex CIII2, focus-refined of type II, Wild type mouse under cold temperature
Method: EM (single particle) / Resolution: 3.8 Å

EMDB-35352: Respiratory complex CI:CIII2, type I, PERK -/- mouse under cold temperature
Method: EM (single particle) / Resolution: 6.3 Å

EMDB-35353: Respiratory complex Peripheral Arm of CI, focus-refined map of type I, PERK -/- mouse under cold temperature
Method: EM (single particle) / Resolution: 3.2 Å

EMDB-35354, PDB-8ic4:
Respiratory complex Membrane domain of CI, focus-refined of type I, PERK -/- mouse under cold temperature
Method: EM (single particle) / Resolution: 3.2 Å

EMDB-35355, PDB-8ic5:
Respiratory complex CIII2, focus-refined of type I, PERK -/- mouse under cold temperature
Method: EM (single particle) / Resolution: 4.1 Å

EMDB-38506, PDB-8xnl:
Respiratory complex Peripheral Arm of CI, close form A, focus-refined map of type I, Wild type mouse under thermoneutral temperature
Method: EM (single particle) / Resolution: 3.1 Å

EMDB-38507, PDB-8xnm:
Respiratory complex Peripheral Arm of CI, close form B, focus-refined map of type I, Wild type mouse under thermoneutral temperature
Method: EM (single particle) / Resolution: 3.5 Å

EMDB-38508, PDB-8xnn:
Respiratory complex Peripheral Arm of CI, open form A, focus-refined map of type I, Wild type mouse under thermoneutral temperature
Method: EM (single particle) / Resolution: 3.6 Å

EMDB-38509, PDB-8xno:
Respiratory complex Peripheral Arm of CI, close form A, focus-refined map of type IA, Wild type mouse under Cold Acclimation
Method: EM (single particle) / Resolution: 3.4 Å

EMDB-38510, PDB-8xnp:
Respiratory complex Peripheral Arm of CI, close form B, focus-refined map of type IA, Wild type mouse under Cold Acclimation
Method: EM (single particle) / Resolution: 3.5 Å

EMDB-38511, PDB-8xnq:
Respiratory complex Peripheral Arm of CI, open form A, focus-refined map of type IA, Wild type mouse under Cold Acclimation
Method: EM (single particle) / Resolution: 3.7 Å

EMDB-38512, PDB-8xnr:
Respiratory complex Peripheral Arm of CI, close form A, focus-refined map of type IB, Wild type mouse under Cold Acclimation
Method: EM (single particle) / Resolution: 3.3 Å

EMDB-38513, PDB-8xns:
Respiratory complex Peripheral Arm of CI, close form B, focus-refined map of type IB, Wild type mouse under Cold Acclimation
Method: EM (single particle) / Resolution: 3.5 Å

EMDB-38514, PDB-8xnt:
Respiratory complex Peripheral Arm of CI, close form C, focus-refined map of type IB, Wild type mouse under Cold Acclimation
Method: EM (single particle) / Resolution: 4.1 Å

EMDB-38515, PDB-8xnu:
Respiratory complex Peripheral Arm of CI, open form A, focus-refined map of type IB, Wild type mouse under Cold Acclimation
Method: EM (single particle) / Resolution: 3.6 Å

EMDB-38516, PDB-8xnv:
Respiratory complex Peripheral Arm of CI, close form A, focus-refined map of type II, Wild type mouse under Cold Acclimation
Method: EM (single particle) / Resolution: 3.3 Å

EMDB-38517, PDB-8xnw:
Respiratory complex Peripheral Arm of CI, close form B, focus-refined map of type II, Wild type mouse under Cold Acclimation
Method: EM (single particle) / Resolution: 3.6 Å

EMDB-38518, PDB-8xnx:
Respiratory complex Peripheral Arm of CI, open form A, focus-refined map of type II, Wild type mouse under Cold Acclimation
Method: EM (single particle) / Resolution: 3.5 Å

EMDB-38519, PDB-8xny:
Respiratory complex Peripheral Arm of CI, open form B, focus-refined map of type II, Wild type mouse under Cold Acclimation
Method: EM (single particle) / Resolution: 4.1 Å

EMDB-38520, PDB-8xnz:
Respiratory complex Peripheral Arm of CI, close form A, focus-refined map of type I, PERK -/- mouse under Cold Acclimation
Method: EM (single particle) / Resolution: 3.3 Å

EMDB-38521, PDB-8xo0:
Respiratory complex Peripheral Arm of CI, close form B, focus-refined map of type I, PERK -/- mouse under Cold Acclimation
Method: EM (single particle) / Resolution: 4.2 Å

Chemicals

ChemComp-3PE:
1,2-Distearoyl-sn-glycerophosphoethanolamine / phospholipid*YM

ChemComp-CDL:
CARDIOLIPIN / phospholipid*YM

ChemComp-SF4:
IRON/SULFUR CLUSTER

ChemComp-UQ1:
UBIQUINONE-1

ChemComp-FES:
FE2/S2 (INORGANIC) CLUSTER

ChemComp-FMN:
FLAVIN MONONUCLEOTIDE

ChemComp-UQ9:
Ubiquinone-9

ChemComp-PC1:
1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE / phospholipid*YM

ChemComp-ADP:
ADENOSINE-5'-DIPHOSPHATE / ADP, energy-carrying molecule*YM

ChemComp-NDP:
NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE

ChemComp-ZN:
Unknown entry

ChemComp-EHZ:
~{S}-[2-[3-[[(2~{R})-3,3-dimethyl-2-oxidanyl-4-phosphonooxy-butanoyl]amino]propanoylamino]ethyl] (3~{S})-3-oxidanyltetradecanethioate

ChemComp-HEM:
PROTOPORPHYRIN IX CONTAINING FE

ChemComp-U10:
UBIQUINONE-10

ChemComp-UQ6:
5-(3,7,11,15,19,23-HEXAMETHYL-TETRACOSA-2,6,10,14,18,22-HEXAENYL)-2,3-DIMETHOXY-6-METHYL-BENZENE-1,4-DIOL

ChemComp-HEC:
HEME C

ChemComp-3PH:
1,2-DIACYL-GLYCEROL-3-SN-PHOSPHATE

Source
  • mus musculus (house mouse)
KeywordsELECTRON TRANSPORT / Respiratory complex / Respiratory supercomplex

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