Regulation of MTOR by Phosphatidic Acid

Overview

Journal Trends Endocrinol Metab

Specialty Endocrinology

Date 2023 Feb 2

PMID 36732094

Authors

Maria A Frias

Ahmet Hatipoglu

David A Foster

Affiliations

Soon will be listed here.

Abstract

mTORC1, the mammalian target of rapamycin complex 1, is a key regulator of cellular physiology. The lipid metabolite phosphatidic acid (PA) binds to and activates mTORC1 in response to nutrients and growth factors. We review structural findings and propose a model for PA activation of mTORC1. PA binds to a highly conserved sequence in the α4 helix of the FK506 binding protein 12 (FKBP12)/rapamycin-binding (FRB) domain of mTOR. It is proposed that PA binding to two adjacent positively charged amino acids breaks and shortens the C-terminal region of helix α4. This has profound consequences for both substrate binding and the catalytic activity of mTORC1.

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