1. Architecture and assembly dynamics of the essential mitochondrial chaperone complex TIM9·10·12
- Author
-
Martha Brennich, Kresten Lindorff-Larsen, Katharina Weinhäupl, Yong Wang, Audrey Hessel, Paul Schanda, Institut de biologie structurale (IBS - UMR 5075), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA), Linderstrøm-Lang Centre for Protein Science [Copenhagen], IT University of Copenhagen (ITU), European Molecular Biology Laboratory [Grenoble] (EMBL), and ANR-18-CE92-0032,MitoMemProtImp,Etudes structurales et fonctionnelles de l'import et le transfert à travers l'espace inter-membranaire des protéines membranaires mitochondriales(2018)
- Subjects
Protein Conformation, alpha-Helical ,0303 health sciences ,Saccharomyces cerevisiae Proteins ,[SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM] ,biology ,Chemistry ,Protein subunit ,030302 biochemistry & molecular biology ,Nuclear magnetic resonance spectroscopy ,03 medical and health sciences ,Membrane ,Mitochondrial biogenesis ,Membrane protein ,Structural Biology ,Chaperone (protein) ,Mitochondrial Precursor Protein Import Complex Proteins ,biology.protein ,Biophysics ,Chaperone complex ,Protein Multimerization ,Molecular Biology ,Dynamic equilibrium ,Protein Binding ,030304 developmental biology - Abstract
Summary Tim chaperones transport membrane proteins to the two mitochondrial membranes. TIM9·10, a 70 kDa protein complex formed by 3 copies of Tim9 and Tim10, guides its clients across the aqueous compartment. The TIM9·10·12 complex is the anchor point at the inner-membrane insertase TIM22. The subunit composition of TIM9·10·12 remains debated. Joint NMR, small-angle X-ray scattering, and MD simulation data allow us to derive a structural model of the TIM9·10·12 assembly, with a 2:3:1 stoichiometry (Tim9:Tim10:Tim12). Both TIM9·10 and TIM9·10·12 hexamers are in a dynamic equilibrium with their constituent subunits, exchanging on a minutes timescale. NMR data establish that the subunits exhibit large conformational dynamics: when the conserved cysteines of the CX3C-Xn-CX3C motifs are formed, short α helices are formed, and these are fully stabilized only upon formation of the mature hexameric chaperone. We propose that the continuous subunit exchange allows mitochondria to control their level of inter-membrane space chaperones.
- Published
- 2021
- Full Text
- View/download PDF