National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
R01GM071940
米国
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
R01AI101057
米国
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
R01GM074830
米国
National Science Foundation (NSF, United States)
DMR-1548924
米国
National Institutes of Health/National Center for Research Resources (NIH/NCRR)
S10RR23057
米国
National Institutes of Health/Office of the Director
S10OD018111
米国
National Science Foundation (NSF, United States)
DBI-133813
米国
引用
ジャーナル: Structure / 年: 2023 タイトル: Discovery, structure, and function of filamentous 3-methylcrotonyl-CoA carboxylase. 著者: Jason J Hu / Jane K J Lee / Yun-Tao Liu / Clinton Yu / Lan Huang / Inna Aphasizheva / Ruslan Aphasizhev / Z Hong Zhou / 要旨: 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 ...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.