6EMK

Cryo-EM Structure of Saccharomyces cerevisiae Target of Rapamycin Complex 2

Summary for 6EMK

• Entry DOI: 10.2210/pdb6emk/pdb
• EMDB information: 2990 3896
• Descriptor: Serine/threonine-protein kinase TOR2, Target of rapamycin complex subunit LST8, Target of rapamycin complex 2 subunit TSC11, ... (5 entities in total)
• Functional Keywords: target of rapamycin, torc2, frb domain, tor2-lst8, kinases, signaling protein
• Biological source: Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast); More
• Total number of polymer chains: 10
• Total formula weight: 1041139.78

Authors

Karuppasamy, M.,Kusmider, B.,Oliveira, T.M.,Gaubitz, C.,Prouteau, M.,Loewith, R.,Schaffitzel, C. (deposition date: 2017-10-02, release date: 2017-12-06, Last modification date: 2024-05-15)

Primary citation

Karuppasamy, M.,Kusmider, B.,Oliveira, T.M.,Gaubitz, C.,Prouteau, M.,Loewith, R.,Schaffitzel, C.
Cryo-EM structure of Saccharomyces cerevisiae target of rapamycin complex 2.
Nat Commun, 8:1729-1729, 2017

PubMed Abstract: The target of rapamycin (TOR) kinase assembles into two distinct multiprotein complexes, conserved across eukaryote evolution. In contrast to TOR complex 1 (TORC1), TORC2 kinase activity is not inhibited by the macrolide rapamycin. Here, we present the structure of Saccharomyces cerevisiae TORC2 determined by electron cryo-microscopy. TORC2 contains six subunits assembling into a 1.4 MDa rhombohedron. Tor2 and Lst8 form the common core of both TOR complexes. Avo3/Rictor is unique to TORC2, but interacts with the same HEAT repeats of Tor2 that are engaged by Kog1/Raptor in mammalian TORC1, explaining the mutual exclusivity of these two proteins. Density, which we conclude is Avo3, occludes the FKBP12-rapamycin-binding site of Tor2's FRB domain rendering TORC2 rapamycin insensitive and recessing the kinase active site. Although mobile, Avo1/hSin1 further restricts access to the active site as its conserved-region-in-the-middle (CRIM) domain is positioned along an edge of the TORC2 active-site-cleft, consistent with a role for CRIM in substrate recruitment.

PubMed: 29170376
DOI: 10.1038/s41467-017-01862-0

Experimental method

ELECTRON MICROSCOPY (7.9 Å)