Tom70 is a mitochondrial protein import receptor composed of 11 tetratricopeptide repeats (TPRs). The first three TPRs form an N-terminal domain that recruits heat shock protein family chaperones, while the eight C-terminal TPRs form a domain that receives, from the bound chaperone, mitochondrial precursor proteins destined for import. Analytical ultracentrifugation and solution small-angle X-ray scattering (SAXS) analysis characterized Tom70 as an elongated monomer. A model for the Tom70 monomer was proposed based on the alternate interpretation of the domain pairings observed in the crystal structure of the Tom70 dimer and refined against the SAXS data. In this "open" model of the Tom70 monomer, the chaperone- and precursor-binding sites are exposed and lay side by side on one face of the molecule. Fluorescence anisotropy measurements indicated that monomeric Tom70 can bind both chaperone and precursor peptides and that chaperone peptide binding does not alter the affinity of Tom70 for the precursor peptide. SAXS was unable to detect any shape change in Tom70 upon chaperone binding. However, molecular modeling indicated that chaperone binding is incompatible with Tom70 dimer formation. It is proposed that the Tom70 monomer is the functional unit mediating initial chaperone docking and precursor recognition.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.jmb.2009.03.070 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Structural characterization of SARS-CoV-2 dimeric ORF9b reveals potential fold-switching trigger mechanism.
Sci China Life Sci
January 2023
School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230027, China.
The constant emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants indicates the evolution and adaptation of the virus. Enhanced innate immune evasion through increased expression of viral antagonist proteins, including ORF9b, contributes to the improved transmission of the Alpha variant; hence, more attention should be paid to these viral proteins. ORF9b is an accessory protein that suppresses innate immunity via a monomer conformation by binding to Tom70.
View Article and Find Full Text PDFStoichiometry and thermodynamics of the interaction between the C-terminus of human 90kDa heat shock protein Hsp90 and the mitochondrial translocase of outer membrane Tom70.
Arch Biochem Biophys
September 2011
Institute of Chemistry, University of Campinas (UNICAMP), 13083-970 Campinas, SP, Brazil.
A large majority of the 1000-1500 proteins in the mitochondria are encoded by the nuclear genome, and therefore, they are translated in the cytosol in the form and contain signals to enable the import of proteins into the organelle. The TOM complex is the major translocase of the outer membrane responsible for preprotein translocation. It consists of a general import pore complex and two membrane import receptors, Tom20 and Tom70.
View Article and Find Full Text PDFHuman mitochondrial import receptor Tom70 functions as a monomer.
Biochem J
August 2010
Department of Biochemistry, McGill University, Montreal, Quebec, Canada.
The mitochondrial import receptor Tom70 (translocase of the mitochondrial outer membrane 70) interacts with chaperone-preprotein complexes through two domains: one that binds Hsp70 (heat-shock protein 70)/Hsc70 (heat-shock cognate 70) and Hsp90, and a second that binds preproteins. The oligomeric state of Tom70 has been controversial, with evidence for both monomeric and homodimeric forms. In the present paper, we report that the functional state of human Tom70 appears to be a monomer with mechanistic implications for its function in mitochondrial protein import.
View Article and Find Full Text PDFDomain organization of the monomeric form of the Tom70 mitochondrial import receptor.
J Mol Biol
May 2009
Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Victoria, Australia.
Tom70 is a mitochondrial protein import receptor composed of 11 tetratricopeptide repeats (TPRs). The first three TPRs form an N-terminal domain that recruits heat shock protein family chaperones, while the eight C-terminal TPRs form a domain that receives, from the bound chaperone, mitochondrial precursor proteins destined for import. Analytical ultracentrifugation and solution small-angle X-ray scattering (SAXS) analysis characterized Tom70 as an elongated monomer.
View Article and Find Full Text PDFA biophysical analysis of the tetratricopeptide repeat-rich mitochondrial import receptor, Tom70, reveals an elongated monomer that is inherently flexible, unstable, and unfolds via a multistate pathway.
J Biol Chem
November 2004
Protein Crystallography Unit, The ARC Centre for Structural and Functional Microbial Genomics, School of Biomedical Sciences, Monash University, Clayton, Victoria 3800, Australia.
Proteins destined for all submitochondrial compartments are translocated across the outer mitochondrial membrane by the TOM (translocase of the outer membrane) complex, which consists of a number of specialized receptor subunits that bind mitochondrial precursor proteins for delivery into the translocation channel. One receptor, Tom70, binds large, hydrophobic mitochondrial precursors. The current model of Tom70-mediated import involves multiple dimers of the receptor recognizing a single molecule of substrate.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!