8F41

3-methylcrotonyl-CoA carboxylase in filament, alpha-subunit centered

Summary for 8F41

• Entry DOI: 10.2210/pdb8f41/pdb
• EMDB information: 28849
• Descriptor: 3-methylcrotonyl-CoA carboxylase, beta-subunit, 3-methylcrotonyl-CoA carboxylase, alpha-subunit, 5-(HEXAHYDRO-2-OXO-1H-THIENO[3,4-D]IMIDAZOL-6-YL)PENTANAL (3 entities in total)
• Functional Keywords: enzyme, multienzyme, multi-enzyme, biotin-dependent, leucine catabolism, protein fibril, ligase
• Biological source: Leishmania tarentolae (Sauroleishmania tarentolae); More
• Total number of polymer chains: 12
• Total formula weight: 823863.93

Authors

Hu, J.J.,Lee, J.K.J.,Liu, Y.T.,Yu, C.,Huang, L.,Afasizheva, I.,Afasizhev, R.,Zhou, Z.H. (deposition date: 2022-11-10, release date: 2023-01-11, Last modification date: 2024-06-19)

Primary citation

Hu, J.J.,Lee, J.K.J.,Liu, Y.T.,Yu, C.,Huang, L.,Aphasizheva, I.,Aphasizhev, R.,Zhou, Z.H.
Discovery, structure, and function of filamentous 3-methylcrotonyl-CoA carboxylase.
Structure, 31:100-110.e4, 2023

PubMed Abstract: 3-methylcrotonyl-CoA carboxylase (MCC) is a biotin-dependent mitochondrial enzyme necessary for leucine catabolism in most organisms. While the crystal structure of recombinant bacterial MCC has been characterized, the structure and potential polymerization of native MCC remain elusive. Here, we discovered that native MCC from Leishmania tarentolae (LtMCC) forms filaments, and determined the structures of different filament regions at 3.4, 3.9, and 7.3 Å resolution using cryoEM. αβ LtMCCs assemble in a twisted-stacks architecture, manifesting as supramolecular rods up to 400 nm. Filamentous LtMCCs bind biotin non-covalently and lack coenzyme A. Filaments elongate by stacking αβ LtMCCs onto the exterior α-trimer of the terminal LtMCC. This stacking immobilizes the biotin carboxylase domains, sequestering the enzyme in an inactive state. Our results support a new model for LtMCC catalysis, termed the dual-swinging-domains model, and cast new light on the function of polymerization in the carboxylase superfamily and beyond.

PubMed: 36543169
DOI: 10.1016/j.str.2022.11.015

Experimental method

ELECTRON MICROSCOPY (3.9 Å)