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Structure paper

TitleHigh-Resolution Structural Proteomics of Mitochondria Using the 'Build and Retrieve' Methodology.
Journal, issue, pagesMol Cell Proteomics, Vol. 22, Issue 12, Page 100666, Year 2023
Publish dateOct 14, 2023
AuthorsZhemin Zhang / Marios L Tringides / Christopher E Morgan / Masaru Miyagi / Jason A Mears / Charles L Hoppel / Edward W Yu /
PubMed AbstractThe application of integrated systems biology to the field of structural biology is a promising new direction, although it is still in the infant stages of development. Here we report the use of ...The application of integrated systems biology to the field of structural biology is a promising new direction, although it is still in the infant stages of development. Here we report the use of single particle cryo-EM to identify multiple proteins from three enriched heterogeneous fractions prepared from human liver mitochondrial lysate. We simultaneously identify and solve high-resolution structures of nine essential mitochondrial enzymes with key metabolic functions, including fatty acid catabolism, reactive oxidative species clearance, and amino acid metabolism. Our methodology also identified multiple distinct members of the acyl-CoA dehydrogenase family. This work highlights the potential of cryo-EM to explore tissue proteomics at the atomic level.
External linksMol Cell Proteomics / PubMed:37839702 / PubMed Central
MethodsEM (single particle)
Resolution2.31 - 3.15 Å
Structure data

EMDB-40463, PDB-8sgp:
human liver mitochondrial Medium-chain specific acyl-CoA dehydrogenase
Method: EM (single particle) / Resolution: 2.69 Å

EMDB-40465, PDB-8sgr:
human liver mitochondrial Isovaleryl-CoA dehydrogenase
Method: EM (single particle) / Resolution: 2.84 Å

EMDB-40466, PDB-8sgs:
human liver mitochondrial Short-chain specific acyl-CoA dehydrogenase
Method: EM (single particle) / Resolution: 3.15 Å

EMDB-40469, PDB-8sgv:
human liver mitochondrial Catalase
Method: EM (single particle) / Resolution: 2.58 Å

EMDB-40493, PDB-8shs:
human liver mitochondrial Aldehyde dehydrogenase ALDH2
Method: EM (single particle) / Resolution: 2.66 Å

EMDB-40556, PDB-8sk6:
human liver mitochondrial Delta(3,5)-Delta(2,4)-dienoyl-CoA isomerase
Method: EM (single particle) / Resolution: 2.96 Å

EMDB-40558, PDB-8sk8:
human liver mitochondrial Glutamate dehydrogenase 1
Method: EM (single particle) / Resolution: 2.31 Å

EMDB-40565, PDB-8skr:
human liver mitochondrial Aspartate aminotransferase
Method: EM (single particle) / Resolution: 2.99 Å

EMDB-40566, PDB-8sks:
human liver mitochondrial Superoxide dismutase [Mn]
Method: EM (single particle) / Resolution: 2.91 Å

Chemicals

ChemComp-FAD:
FLAVIN-ADENINE DINUCLEOTIDE / FAD*YM / Flavin adenine dinucleotide

ChemComp-COA:
COENZYME A / Coenzyme A

ChemComp-HEM:
PROTOPORPHYRIN IX CONTAINING FE / Heme B

ChemComp-NDP:
NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE / Nicotinamide adenine dinucleotide phosphate

ChemComp-PLP:
PYRIDOXAL-5'-PHOSPHATE / Pyridoxal phosphate

ChemComp-MN:
Unknown entry

Source
  • homo sapiens (human)
KeywordsOXIDOREDUCTASE / human / liver / mitochondrial / Medium-chain specific acyl-CoA dehydrogenase / Isovaleryl-CoA dehydrogenase / Short-chain specific acyl-CoA dehydrogenase / Catalase / Aldehyde dehydrogenase / ALDH2 / ISOMERASE / Delta(3 / 5)-Delta(2 / 4)-dienoyl-CoA isomerase / Glutamate dehydrogenase 1 / TRANSFERASE / Aspartate aminotransferase / Superoxide dismutase [Mn]

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