IMB Seminar Series – Dr James Letts – ‘Cryo-EM structural studies of Mammalian Mitochondrial Respiratory Supercomplexes’
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- Mitochondrial electron transport chain complexes I, III and IV are organized into supercomplexes responsible for carrying out cellular respiration. Using electron cryo-microscopy, three architectures of mammalian (sheep) supercomplexes were determined. Distinct arrangements of supercomplex I+III2+IV (the respirasome)—a major \'tight\' form and a minor \'loose\' form (resolved at the resolution of 5.8 Å and 6.7 Å, respectively) were solved along with a supercomplex I+III2 at 7.8 Å resolution. Along side we also determined the first nearly complete atomic structure of isolated mitochondrial complex I at 3.9 Å resolution. With this structure and the known crystal structures of isolated complex III2 and complex IV all observed density in the respirasome could be attributed to the known 80 subunits of the individual complexes, including 132 transmembrane helices. Together these represent the first complete architectures of the dominant, physiologically relevant state of the electron transport chain. More recently, using a novel preparation of functional mitochondrial supercomplex I+III2 this structure has now been resolved to 4.0 Å resolution with multiple supercomplex classes showing alternate conformation around the quinone binding site of complex I indicative of an active to deactive transition.
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