Tor forms a dimer through an N-terminal helical solenoid with a complex topology
| Autor: | Alex Berndt, Christopher M. Johnson, Domagoj Baretić, Roger L. Williams, Yohei Ohashi |
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| Rok vydání: | 2016 |
| Předmět: |
Models
Molecular 0301 basic medicine Saccharomyces cerevisiae Proteins Science Protein subunit Dimer General Physics and Astronomy Mechanistic Target of Rapamycin Complex 2 Saccharomyces cerevisiae Plasma protein binding Solenoid (DNA) Mechanistic Target of Rapamycin Complex 1 Biology Topology Protein Structure Secondary Article General Biochemistry Genetics and Molecular Biology Kluyveromyces Mice 03 medical and health sciences chemistry.chemical_compound Protein structure Catalytic Domain Animals Humans Transferase Protein kinase A Multidisciplinary TOR Serine-Threonine Kinases Cryoelectron Microscopy General Chemistry Protein Structure Tertiary 030104 developmental biology chemistry Multiprotein Complexes Protein Multimerization Protein Binding |
| Zdroj: | Nature Communications Nature Communications, Vol 7, Iss 1, Pp 1-9 (2016) |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/ncomms11016 |
| Popis: | The target of rapamycin (Tor) is a Ser/Thr protein kinase that regulates a range of anabolic and catabolic processes. Tor is present in two complexes, TORC1 and TORC2, in which the Tor–Lst8 heterodimer forms a common sub-complex. We have determined the cryo-electron microscopy (EM) structure of Tor bound to Lst8. Two Tor–Lst8 heterodimers assemble further into a dyad-symmetry dimer mediated by Tor–Tor interactions. The first 1,300 residues of Tor form a HEAT repeat-containing α-solenoid with four distinct segments: a highly curved 800-residue N-terminal 'spiral', followed by a 400-residue low-curvature 'bridge' and an extended ‘railing' running along the bridge leading to the 'cap' that links to FAT region. This complex topology was verified by domain insertions and offers a new interpretation of the mTORC1 structure. The spiral of one TOR interacts with the bridge of another, which together form a joint platform for the Regulatory Associated Protein of TOR (RAPTOR) regulatory subunit. The target of rapamycin (Tor) is a Ser/Thr protein kinase that regulates a wide range of anabolic and catabolic processes. Here the authors describe a sub-nanometer cryo-EM structure of a yeast Tor–Lst8 complex and propose an overall topology that differs from that previously suggested for mTORC1. |
| Databáze: | OpenAIRE |
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