7dkl
From Proteopedia
Crystal structure of the tandem DEP domains of DEPTOR
Structural highlights
FunctionDPTOR_HUMAN Negative regulator of the mTORC1 and mTORC2 signaling pathways. Inhibits the kinase activity of both complexes.[1] Publication Abstract from PubMedDEP domain containing mTOR-interacting protein (DEPTOR) plays pivotal roles in regulating metabolism, growth, autophagy and apoptosis by functions as an endogenous inhibitor of mTOR signaling pathway. Activated by phosphatidic acid, a second messenger in mTOR signaling, DEPTOR dissociates from mTORC1 complex with unknown mechanism. Here, we present a 1.5 A resolution crystal structure, which shows that the N-terminal two tandem DEP domains of hDEPTOR fold into a dumbbell-shaped structure, protruding the characteristic beta-hairpin arms of DEP domains on each side. An 18 amino acids DDEX motif at the end of DEP2 interacts with DEP1 and stabilizes the structure. Biochemical studies showed that the tandem DEP domains directly interact with phosphatidic acid using two distinct positively charged patches. These results provide insights into mTOR activation upon phosphatidic acid stimulation. Structural Basis of DEPTOR to Recognize Phosphatidic Acid Using its Tandem DEP Domains.,Weng Z, Shen X, Zheng J, Liang H, Liu Y J Mol Biol. 2021 Jun 25;433(13):166989. doi: 10.1016/j.jmb.2021.166989. Epub 2021, Apr 16. PMID:33865870[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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