PMID- 34519268
OWN - NLM
STAT- MEDLINE
DCOM- 20211027
LR  - 20240403
IS  - 2050-084X (Electronic)
IS  - 2050-084X (Linking)
VI  - 10
DP  - 2021 Sep 14
TI  - Regulation of human mTOR complexes by DEPTOR.
LID - 10.7554/eLife.70871 [doi]
LID - e70871
AB  - The vertebrate-specific DEP domain-containing mTOR interacting protein (DEPTOR), 
      an oncoprotein or tumor suppressor, has important roles in metabolism, immunity, 
      and cancer. It is the only protein that binds and regulates both complexes of 
      mammalian target of rapamycin (mTOR), a central regulator of cell growth. 
      Biochemical analysis and cryo-EM reconstructions of DEPTOR bound to human mTOR 
      complex 1 (mTORC1) and mTORC2 reveal that both structured regions of DEPTOR, the 
      PDZ domain and the DEP domain tandem (DEPt), are involved in mTOR interaction. 
      The PDZ domain binds tightly with mildly activating effect, but then acts as an 
      anchor for DEPt association that allosterically suppresses mTOR activation. The 
      binding interfaces of the PDZ domain and DEPt also support further regulation by 
      other signaling pathways. A separate, substrate-like mode of interaction for 
      DEPTOR phosphorylation by mTOR complexes rationalizes inhibition of 
      non-stimulated mTOR activity at higher DEPTOR concentrations. The multifaceted 
      interplay between DEPTOR and mTOR provides a basis for understanding the 
      divergent roles of DEPTOR in physiology and opens new routes for targeting the 
      mTOR-DEPTOR interaction in disease.
CI  - (c) 2021, Walchli et al.
FAU - Walchli, Matthias
AU  - Walchli M
AUID- ORCID: 0000-0001-9354-3079
AD  - Biozentrum, University of Basel, Basel, Switzerland.
FAU - Berneiser, Karolin
AU  - Berneiser K
AUID- ORCID: 0000-0002-0963-8559
AD  - Biozentrum, University of Basel, Basel, Switzerland.
FAU - Mangia, Francesca
AU  - Mangia F
AUID- ORCID: 0000-0001-5430-397X
AD  - Biozentrum, University of Basel, Basel, Switzerland.
FAU - Imseng, Stefan
AU  - Imseng S
AUID- ORCID: 0000-0002-0248-0795
AD  - Biozentrum, University of Basel, Basel, Switzerland.
FAU - Craigie, Louise-Marie
AU  - Craigie LM
AD  - Biozentrum, University of Basel, Basel, Switzerland.
FAU - Stuttfeld, Edward
AU  - Stuttfeld E
AUID- ORCID: 0000-0003-3932-9076
AD  - Biozentrum, University of Basel, Basel, Switzerland.
FAU - Hall, Michael N
AU  - Hall MN
AUID- ORCID: 0000-0002-2998-0757
AD  - Biozentrum, University of Basel, Basel, Switzerland.
FAU - Maier, Timm
AU  - Maier T
AUID- ORCID: 0000-0002-7459-1363
AD  - Biozentrum, University of Basel, Basel, Switzerland.
LA  - eng
GR  - 141735/SNSF_/Swiss National Science Foundation/Switzerland
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210914
PL  - England
TA  - Elife
JT  - eLife
JID - 101579614
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - EC 2.7.1.1 (DEPTOR protein, human)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - Cell Line
MH  - Cryoelectron Microscopy
MH  - Crystallography, X-Ray
MH  - Gene Expression Regulation/*physiology
MH  - Humans
MH  - Intracellular Signaling Peptides and Proteins/genetics/*metabolism
MH  - Moths
MH  - Protein Domains
MH  - TOR Serine-Threonine Kinases/genetics/*metabolism
PMC - PMC8439649
OTO - NOTNLM
OT  - DEPTOR
OT  - cancer
OT  - cryo-EM
OT  - human
OT  - mTOR
OT  - metabolism
OT  - molecular biophysics
OT  - signaling
OT  - structural biology
COIS- MW, KB, FM, SI, LC, ES, MH, TM None
EDAT- 2021/09/15 06:00
MHDA- 2021/10/28 06:00
PMCR- 2021/09/14
CRDT- 2021/09/14 08:41
PHST- 2021/06/01 00:00 [received]
PHST- 2021/07/31 00:00 [accepted]
PHST- 2021/09/14 08:41 [entrez]
PHST- 2021/09/15 06:00 [pubmed]
PHST- 2021/10/28 06:00 [medline]
PHST- 2021/09/14 00:00 [pmc-release]
AID - 70871 [pii]
AID - 10.7554/eLife.70871 [doi]
PST - epublish
SO  - Elife. 2021 Sep 14;10:e70871. doi: 10.7554/eLife.70871.