Structure of TOR and Its Complex with KOG1

Alessandra Adami, Begoña García-Álvarez, Ernesto Arias-Palomo, David Barford, Oscar Llorca

Research output: Contribution to journalArticle

Abstract

The target of rapamycin (TOR) is a large (281 kDa) conserved Ser/Thr protein kinase that functions as a central controller of cell growth. TOR assembles into two distinct multiprotein complexes: TORC1 and TORC2. A defining feature of TORC1 is the interaction of TOR with KOG1 (Raptor in mammals) and its sensitivity to a rapamycin-FKBP12 complex. Here, we have reconstructed in three dimensions the 25 Å resolution structures of endogenous budding yeast TOR1 and a TOR-KOG1 complex, using electron microscopy. TOR features distinctive N-terminal HEAT repeats that form a curved tubular-shaped domain that associates with the C-terminal WD40 repeat domain of KOG1. The N terminus of KOG1 is in proximity to the TOR kinase domain, likely functioning to bring substrates into the vicinity of the catalytic region. A model is proposed for the molecular architecture of the TOR-KOG1 complex explaining its sensitivity to rapamycin.

Original languageEnglish (US)
Pages (from-to)509-516
Number of pages8
JournalMolecular Cell
Volume27
Issue number3
DOIs
StatePublished - Aug 3 2007
Externally publishedYes

Fingerprint

Sirolimus
Terminal Repeat Sequences
Tacrolimus Binding Protein 1A
Raptors
Multiprotein Complexes
Saccharomycetales
Protein Kinases
Mammals
Catalytic Domain
Electron Microscopy
Phosphotransferases
Growth

Keywords

  • CELLCYCLE
  • SIGNALING

ASJC Scopus subject areas

  • Molecular Biology

Cite this

Adami, A., García-Álvarez, B., Arias-Palomo, E., Barford, D., & Llorca, O. (2007). Structure of TOR and Its Complex with KOG1. Molecular Cell, 27(3), 509-516. https://doi.org/10.1016/j.molcel.2007.05.040

Structure of TOR and Its Complex with KOG1. / Adami, Alessandra; García-Álvarez, Begoña; Arias-Palomo, Ernesto; Barford, David; Llorca, Oscar.

In: Molecular Cell, Vol. 27, No. 3, 03.08.2007, p. 509-516.

Research output: Contribution to journalArticle

Adami, A, García-Álvarez, B, Arias-Palomo, E, Barford, D & Llorca, O 2007, 'Structure of TOR and Its Complex with KOG1', Molecular Cell, vol. 27, no. 3, pp. 509-516. https://doi.org/10.1016/j.molcel.2007.05.040
Adami A, García-Álvarez B, Arias-Palomo E, Barford D, Llorca O. Structure of TOR and Its Complex with KOG1. Molecular Cell. 2007 Aug 3;27(3):509-516. https://doi.org/10.1016/j.molcel.2007.05.040
Adami, Alessandra ; García-Álvarez, Begoña ; Arias-Palomo, Ernesto ; Barford, David ; Llorca, Oscar. / Structure of TOR and Its Complex with KOG1. In: Molecular Cell. 2007 ; Vol. 27, No. 3. pp. 509-516.
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