CoChat
Sign Up
Cited by 105

The DOI matches its Crossref record; 7 of the 7 references it cites were found in a registry or an index.

The 3.2-Å resolution structure of human mTORC2

Scaiola, Alain, Mangia, Francesca, Imseng, Stefan, Boehringer, Daniel, Berneiser, Karolin, Shimobayashi, Mitsugu, Stuttfeld, Edward, Hall, Michael N., Ban, Nenad, Maier, Timm·2020·Science Advances
DOI 10.1126/sciadv.abc1251PMC PMC7673708
Open this paper in CoChat — free account

Abstract

The structure of mTORC2 reveals the basis of its rapamycin insensitivity and explains how mTORC2 stability controls activity.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1126/sciadv.abc1251

Cites

7 of 7 references verified0 citation errors · 0 not checkable

Statistics

Figures

Fig. 1 Structure of mTOR complex 2. (A) Sequence-level domain organization of mTOR. Modeled and unresolved regions are indicated as dotted lines. Interactions with other proteins in the complex are highlighted below the sequences. (B) Density of the overall cryo-EM reconstruction of mTORC2 colored according to protein subunits and mTOR domains as indicated. The top half is better resolved than the lower one, most likely due to conformational flexibility. (C) Cartoon representation of mTORC2 in three different orientations. The proteins Rictor (magenta) and SIN1 (green) are unique to mTORC2, while mTOR (colored by domain) and mLST8 (orange) are common to both mTORC1 and mTORC2. Bound ligands are represented as cyan spheres.
Fig. 1 Structure of mTOR complex 2. (A) Sequence-level domain organization of mTOR. Modeled and unresolved regions are indicated as dotted lines. Interactions with other proteins in the complex are highlighted below the sequences. (B) Density of the overall cryo-EM reconstruction of mTORC2 colored according to protein subunits and mTOR domains as indicated. The top half is better resolved than the lower one, most likely due to conformational flexibility. (C) Cartoon representation of mTORC2 in three different orientations. The proteins Rictor (magenta) and SIN1 (green) are unique to mTORC2, while mTOR (colored by domain) and mLST8 (orange) are common to both mTORC1 and mTORC2. Bound ligands are represented as cyan spheres.CC BY-NC · PubMed Central
Fig. 2 The architecture of Rictor. (A) Sequence-level domain organization of Rictor. Flexible and unresolved regions are indicated as dotted lines. Interactions with other proteins in the complex are highlighted below the sequences. Asterisks indicate residues interacting with the N-terminal region of SIN1. (B) Two views of Rictor, colored by domains. The structured part of Rictor forms three domains: an N-terminal Armadillo repeat domain (AD, magenta), a HEAT-like repeat domain (HD, dark magenta), and a C-terminal domain (CD, light red); the phosphorylation site region (PR) remains disordered. The sequences flanking the nonresolved PR are highlighted in red, and the PR anchor is colored in gold. Bound ligands are shown as cyan spheres. (C) Schematic representation of Rictor and SIN1 domain topology. (D) The Rictor CD occupies the FRB domain and sterically blocks FKBP-rapamycin binding (26).
Fig. 2 The architecture of Rictor. (A) Sequence-level domain organization of Rictor. Flexible and unresolved regions are indicated as dotted lines. Interactions with other proteins in the complex are highlighted below the sequences. Asterisks indicate residues interacting with the N-terminal region of SIN1. (B) Two views of Rictor, colored by domains. The structured part of Rictor forms three domains: an N-terminal Armadillo repeat domain (AD, magenta), a HEAT-like repeat domain (HD, dark magenta), and a C-terminal domain (CD, light red); the phosphorylation site region (PR) remains disordered. The sequences flanking the nonresolved PR are highlighted in red, and the PR anchor is colored in gold. Bound ligands are shown as cyan spheres. (C) Schematic representation of Rictor and SIN1 domain topology. (D) The Rictor CD occupies the FRB domain and sterically blocks FKBP-rapamycin binding (26).CC BY-NC · PubMed Central
Fig. 3 The SIN1 N-terminal region is an integral component of mTORC2. (A) Sequence-level domain organization of SIN1. Flexible and unresolved regions are shown above each domain representation as dotted lines in two colors as indicated. Interactions with other proteins in the complex are indicated below the domain representation. (B) Extension of the processed SIN1 N terminus disrupts assembly of Rictor and SIN1 with mTOR/mLST8 into mTORC2. SDS-polyacrylamide gel of a FLAG bead pulldown from lysates of insect cells expressing mTORC2 comprising SIN1 variants. Levels of Rictor are drastically reduced in the mTOR-based pulldown for mTORC2 carrying variants of SIN1 N-terminally extended by a tryptophan (mTORC2 SIN1_W), two consecutive arginines (mTORC2 SIN1_2R), and three consecutive arginines (mTORC2 SIN1_3R). (C) Surface representation of mTORC2. SIN1 (shown as green cartoon) interacts via two N-terminal helices with Rictor, winds around Rictor, traverses the catalytic site cleft, and winds around mLST8. The field of view of subpanel D is indicated. (D) Close-up view of the SIN1 N-terminal residues, which are deeply inserted between Rictor AD and HD. Acetylated Ala2 and Phe3 are bound in a hydrophobic pocket, while Asp5 interacts via salt bridges (yellow dashes). (E) Top view of mLST8 β-propeller (orange) and the interaction regions with SIN1 (green). The nomenclature for WD40 β-propeller repeats is indicated. (F) Top view of the catalytic site with the structure shown as surface together with the density of a subclass (light gray). The lower-resolution extra density is consistent with a placement of the SIN1 CRIM domain, here shown in dark green (PDB: 2RVK). Unassigned extra density protrudes from the CRIM domain to the mTOR active site and Rictor.
Fig. 3 The SIN1 N-terminal region is an integral component of mTORC2. (A) Sequence-level domain organization of SIN1. Flexible and unresolved regions are shown above each domain representation as dotted lines in two colors as indicated. Interactions with other proteins in the complex are indicated below the domain representation. (B) Extension of the processed SIN1 N terminus disrupts assembly of Rictor and SIN1 with mTOR/mLST8 into mTORC2. SDS-polyacrylamide gel of a FLAG bead pulldown from lysates of insect cells expressing mTORC2 comprising SIN1 variants. Levels of Rictor are drastically reduced in the mTOR-based pulldown for mTORC2 carrying variants of SIN1 N-terminally extended by a tryptophan (mTORC2 SIN1_W), two consecutive arginines (mTORC2 SIN1_2R), and three consecutive arginines (mTORC2 SIN1_3R). (C) Surface representation of mTORC2. SIN1 (shown as green cartoon) interacts via two N-terminal helices with Rictor, winds around Rictor, traverses the catalytic site cleft, and winds around mLST8. The field of view of subpanel D is indicated. (D) Close-up view of the SIN1 N-terminal residues, which are deeply inserted between Rictor AD and HD. Acetylated Ala2 and Phe3 are bound in a hydrophobic pocket, while Asp5 interacts via salt bridges (yellow dashes). (E) Top view of mLST8 β-propeller (orange) and the interaction regions with SIN1 (green). The nomenclature for WD40 β-propeller repeats is indicated. (F) Top view of the catalytic site with the structure shown as surface together with the density of a subclass (light gray). The lower-resolution extra density is consistent with a placement of the SIN1 CRIM domain, here shown in dark green (PDB: 2RVK). Unassigned extra density protrudes from the CRIM domain to the mTOR active site and Rictor.CC BY-NC · PubMed Central
Fig. 4 Small-molecule binding sites of mTORC2 outside the active site region. (A) Overview of mTORC2 architecture and ligand interaction sites. Each half of the dimeric mTORC2 has three small-molecule binding sites. The kinase active site and the A-site, which is located in the peripheral region of Rictor, bind to ATP (or ATP analogs). The I-site in the middle of the FAT domain of mTOR binds InsP6. The indicated modifications on SIN1 and mLST8 affect mTORC2 assembly. Extra-density region following the CRIM domain is indicated as a gray outline. (B). Close-up view of the A-site on the periphery of the Rictor HD with bound ATPγS. A hydrogen bond between ATPγS and Asn543 is shown as dashed yellow lines. (C) Close-up view of the I-site in the FAT domain of mTOR. InsP6 is surrounded by a cluster of positively charged amino acids. It only directly interacts with residues of the FAT domain.
Fig. 4 Small-molecule binding sites of mTORC2 outside the active site region. (A) Overview of mTORC2 architecture and ligand interaction sites. Each half of the dimeric mTORC2 has three small-molecule binding sites. The kinase active site and the A-site, which is located in the peripheral region of Rictor, bind to ATP (or ATP analogs). The I-site in the middle of the FAT domain of mTOR binds InsP6. The indicated modifications on SIN1 and mLST8 affect mTORC2 assembly. Extra-density region following the CRIM domain is indicated as a gray outline. (B). Close-up view of the A-site on the periphery of the Rictor HD with bound ATPγS. A hydrogen bond between ATPγS and Asn543 is shown as dashed yellow lines. (C) Close-up view of the I-site in the FAT domain of mTOR. InsP6 is surrounded by a cluster of positively charged amino acids. It only directly interacts with residues of the FAT domain.CC BY-NC · PubMed Central

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Show all 7 references

Research works printed but not linked: 55

  1. 10.1038/s41568-018-0074-8 · DOI · Paper page
  2. 10.1016/j.sbi.2018.03.010 · DOI
  3. 10.1126/science.270.5233.50 · DOI
  4. 10.1016/S0092-8674(02)00833-4 · DOI
  5. 10.1016/S1097-2765(03)00114-X · DOI
  6. 10.1016/j.cub.2004.06.054 · DOI · Paper page
  7. 10.1101/gad.1461206 · DOI
  8. 10.1042/BJ20070540 · DOI
  9. 10.1042/BJ20081668 · DOI · Paper page
  10. 10.1038/emboj.2008.119 · DOI
  11. 10.1126/science.1106148 · DOI · Paper page
  12. 10.1016/j.ccell.2017.11.011 · DOI
  13. 10.1038/nrd3531 · DOI
  14. 10.1371/journal.pone.0176599 · DOI
  15. 10.1038/ncomms11016 · DOI
  16. 10.1038/s41422-018-0029-3 · DOI
  17. 10.1038/s41467-017-01862-0 · DOI
  18. 10.7554/eLife.33101 · DOI
  19. 10.1107/S1744309112007178 · DOI
  20. 10.7554/eLife.19594 · DOI
  21. 10.1007/s10858-014-9882-7 · DOI
  22. 10.1016/j.molcel.2015.04.031 · DOI · Paper page
  23. 10.1128/MCB.00735-09 · DOI
  24. 10.1152/ajpheart.00293.2009 · DOI
  25. 10.1039/C6MT00286B · DOI
  26. 10.1038/ncb2860 · DOI
  27. 10.1158/0008-5472.CAN-18-3658 · DOI
  28. 10.1074/jbc.M505553200 · DOI
  29. 10.1038/nature22344 · DOI
  30. 10.1038/s41594-019-0342-7 · DOI
  31. 10.1016/S0092-8674(00)00061-1 · DOI
  32. 10.1038/s41422-019-0143-x · DOI
  33. 10.1016/j.molcel.2019.07.014 · DOI
  34. 10.1016/j.molcel.2016.02.033 · DOI
  35. 10.1038/nmeth983 · DOI · Paper page
  36. 10.1074/jbc.272.50.31515 · DOI · Paper page
  37. 10.1073/pnas.1716109115 · DOI
  38. 10.1128/mBio.02323-18 · DOI
  39. 10.1038/nmeth.3047 · DOI · Paper page
  40. 10.1021/acs.jproteome.6b00066 · DOI
  41. 10.1021/ac0341261 · DOI
  42. 10.1016/j.jsb.2005.07.007 · DOI
  43. 10.1038/nmeth.4193 · DOI
  44. 10.1016/j.jsb.2015.11.003 · DOI
  45. 10.1006/jsbi.1999.4174 · DOI
  46. 10.1107/S205225251801463X · DOI
  47. 10.1038/nmeth.4169 · DOI · Paper page
  48. 10.1002/jcc.20084 · DOI
  49. 10.1107/S0907444909052925 · DOI · Paper page
  50. 10.1107/S0907444910007493 · DOI · Paper page
  51. 10.1002/pro.3235 · DOI · Paper page
  52. 10.1073/pnas.181342398 · DOI
  53. 10.1038/msb.2011.75 · DOI
  54. 10.1093/bioinformatics/15.4.305 · DOI
  55. 10.1093/bioinformatics/17.8.700 · DOI

Cited by

Sorted by citations

See all 105

Metadata

Authors
Scaiola, A., Mangia, F., Imseng, S., Boehringer, D., Berneiser, K., Shimobayashi, M., Stuttfeld, E., Hall, M. N., Ban, N., & Maier, T.
Affiliations
  • Institute for Molecular Biology and Biophysics, ETH Zurich, Zurich, Switzerland.
  • Biozentrum, University of Basel, Klingelbergstrasse 50/70, 4056 Basel, Switzerland.
  • Cryo-EM Knowledge Hub, ETH Zurich, 8093 Zurich, Switzerland.
ORCID
Venue
Science Advances
Publisher
American Association for the Advancement of Science (AAAS)
Published
2020-11-06
Volume
6
Issue
45
ISSN
2375-2548
DOI
10.1126/sciadv.abc1251
PMC
PMC7673708
Cited by
105
References
7
Language
en
Licence
creativecommons.org/licenses/by-nc/4.0/ (vor)
Funders
  • Swiss National Science Foundation (177084)
  • Fellowship for Excellence from the Biozentrum Basel International PhD program
  • National Center of Excellence in RNA and Disease (138262)
  • Swiss National Science Foundation SNSF (179323)
  • Fellowship of the Biozentrum International PhD Program

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

How to cite

Cite CoChat for the checks on this page, and the paper for its own findings.

This page
CoChat. (2026). Citation check: The 3.2-Å resolution structure of human mTORC2. https://app.cochat.ai/papers/10.1126/sciadv.abc1251
The paper
Scaiola, A., Mangia, F., Imseng, S., Boehringer, D., Berneiser, K., Shimobayashi, M., Stuttfeld, E., Hall, M. N., Ban, N., & Maier, T. (2020). The 3.2-Å resolution structure of human mTORC2. Science Advances. https://doi.org/10.1126/sciadv.abc1251