Crystal structure of the mitochondrial chaperone TIM9.10 reveals a six-bladed alpha-propeller.
Import of proteins into mitochondria occurs by coordinated actions of preprotein translocases in the outer and inner membranes. Tim9 and Tim10 are translocase components of the intermembrane space, related to deafness-dystonia peptide 1 (DDP1). They coassemble into a hexamer, TIM9.10, which captures and chaperones precursors of inner membrane metabolite carriers as they exit the TOM channel in the outer membrane. The crystal structure of TIM9.10 reveals a previously undescribed alpha-propeller topology in which helical "blades" radiate from a narrow central pore lined with polar residues. The propeller blades are reminiscent of "tentacles" in chaperones Skp and prefoldin. In each TIM9.10 subunit, a signature "twin CX3C" motif forms two intramolecular disulfides. There is no obvious binding pocket for precursors, which we suggest employ the chaperone-like tentacles of TIM9.10 as surrogate lipid contacts. The first reported crystal structure of a mitochondrial translocase assembly provides insights into selectivity and regulation of precursor import.
Webb
Chaille T
CT
Structural Biology Division, The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3050, Australia.
Gorman
Michael A
MA
Lazarou
Michael
M
Ryan
Michael T
MT
Gulbis
Jacqueline M
JM
D000595:Amino Acid Sequence; D000818:Animals; D018360:Crystallography, X-Ray; D004220:Disulfides; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006801:Humans; D024101:Mitochondrial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D018832:Molecular Chaperones / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D016415:Sequence Alignment
D004220:Disulfides; D029968:Escherichia coli Proteins; D024101:Mitochondrial Proteins; D018832:Molecular Chaperones; D046912:Multiprotein Complexes; C478387:TIM10 protein, E coli; C478388:TIM9 protein, E coli