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TitleCryoEM reveals oligomeric isomers of a multienzyme complex and assembly mechanics.
Journal, issue, pagesJ Struct Biol X, Vol. 7, Page 100088, Year 2023
Publish dateApr 8, 2023
AuthorsJane K J Lee / Yun-Tao Liu / Jason J Hu / Inna Aphasizheva / Ruslan Aphasizhev / Z Hong Zhou /
PubMed AbstractPropionyl-CoA carboxylase (PCC) is a multienzyme complex consisting of up to six α-subunits and six β-subunits. Belonging to a metabolic pathway converging on the citric acid cycle, it is present ...Propionyl-CoA carboxylase (PCC) is a multienzyme complex consisting of up to six α-subunits and six β-subunits. Belonging to a metabolic pathway converging on the citric acid cycle, it is present in most forms of life and irregularities in its assembly lead to serious illness in humans, known as propionic acidemia. Here, we report the cryogenic electron microscopy (cryoEM) structures and assembly of different oligomeric isomers of endogenous PCC from the parasitic protozoan (LtPCC). These structures and their statistical distribution reveal the mechanics of PCC assembly and disassembly at equilibrium. We show that, in solution, endogenous LtPCC β-subunits form stable homohexamers, to which different numbers of α-subunits attach. Sorting LtPCC particles into seven classes (i.e., oligomeric formulae αβ, αβ, αβ, αβ, αβ, αβ, αβ) enables formulation of a model for PCC assembly. Our results suggest how multimerization regulates PCC enzymatic activity and showcase the utility of cryoEM in revealing the statistical mechanics of reaction pathways.
External linksJ Struct Biol X / PubMed:37128595 / PubMed Central
MethodsEM (single particle)
Resolution3.2 - 10.3 Å
Structure data

40472

8sgx

EMDB-40472, PDB-8sgx:
Leishmania tarentolae propionyl-CoA carboxylase (alpha-4-beta-6)
Method: EM (single particle) / Resolution: 10.3 Å

40473

8sgy

EMDB-40473, PDB-8sgy:
Leishmania tarentolae propionyl-CoA carboxylase (alpha-5-beta-6)
Method: EM (single particle) / Resolution: 8.62 Å

40474

8sgz

EMDB-40474, PDB-8sgz:
Leishmania tarentolae propionyl-CoA carboxylase (alpha-6-beta-6)
Method: EM (single particle) / Resolution: 3.2 Å

Chemicals

ChemComp-BTI:
5-(HEXAHYDRO-2-OXO-1H-THIENO[3,4-D]IMIDAZOL-6-YL)PENTANAL

Source
  • leishmania tarentolae (eukaryote)
KeywordsLIGASE / Multienzyme complex / carboxylase

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