9ZBK

mTORC2 in complex with Akt1

This is a non-PDB format compatible entry.

Summary for 9ZBK

• Entry DOI: 10.2210/pdb9zbk/pdb
• EMDB information: 73991 73992
• Descriptor: Serine/threonine-protein kinase mTOR, Target of rapamycin complex subunit LST8, Rapamycin-insensitive companion of mTOR, ... (7 entities in total)
• Functional Keywords: cellular growth control, transferase, torin
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 5
• Total formula weight: 574416.00

Authors

Wranik, M.,Lee, J.M.,Rogala, K.B. (deposition date: 2025-11-20, release date: 2026-04-15)

Primary citation

Taylor, M.S.,Chen, M.,Hancock, M.,Wranik, M.,Miller, B.D.,O'Meara, T.R.,Palanski, B.A.,Ficarro, S.B.,Groendyke, B.J.,Xiang, Y.,Kondo, K.T.,Linde-Garelli, K.Y.,Lee, M.J.,Mondal, D.,Freund, D.,Congreve, S.,Matas, K.,Hennink, M.,Xibinaku, K.,Valenstein, M.L.,van Eeuwen, T.,Marto, J.A.,Sali, A.,Shi, Y.,Gray, N.S.,Sabatini, D.M.,Chu, N.,Rogala, K.B.,Cole, P.A.
Structural basis for the recruitment and selective phosphorylation of Akt by mTORC2.
Science, 391:eadv7111-eadv7111, 2026

PubMed Abstract: The mechanistic target of rapamycin (mTOR) protein kinase forms two multiprotein complexes, mTORC1 and mTORC2, that function in distinct signaling pathways. mTORC1 is regulated by nutrients, and mTORC2 is a central node in phosphoinositide-3 kinase (PI3K) and small guanosine triphosphate Ras signaling networks commonly deregulated in cancer and diabetes. Although mTOR phosphorylates many substrates in vitro, in cells, mTORC1 and mTORC2 have high specificity: mTORC2 phosphorylates the protein kinases Akt and PKC, but not closely related kinases that are mTORC1 substrates. To understand how mTORC2 recognizes substrates, we created semisynthetic probes to trap the mTORC2 :: Akt complex and determine its structure. Whereas most protein kinases recognize amino acids adjacent to the phosphorylation site, local sequence contributes little to substrate recognition by mTORC2. Instead, the specificity determinants were secondary and tertiary structural elements of Akt that bound the mTORC2 component mSin1 distal to the mTOR active site and were conserved among at least 18 related substrates. These results reveal how mTORC2 recognizes its canonical substrates and may enable the design of mTORC2-specific inhibitors.

PubMed: 41308123
DOI: 10.1126/science.adv7111

Experimental method

ELECTRON MICROSCOPY (2.6 Å)