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Updated: Dec 30, 2025

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants

Published on: June 6, 2025

The structural basis for mTOR function.

Domagoj Baretić¹, Roger L Williams¹

¹Medical Research Council Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK.

Seminars in Cell & Developmental Biology

|October 8, 2014

Summary

This summary is machine-generated.

The protein kinase mTOR

Keywords:

4E-BP1 PI3K PIKK Rapamycin S6K1 mTOR

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Area of Science:

Biochemistry
Molecular Biology
Structural Biology

Background:

The phosphoinositide 3-kinase (PI3K) related protein kinases (PIKKs) are crucial for various cellular functions.
High-resolution crystal structures of mTOR provide insights into PIKK family architecture and PI3K relationships.

Purpose of the Study:

To elucidate the structural basis of mTOR's substrate specificity.
To understand the unique features of mTOR enabling substrate recognition and inhibition.

Main Methods:

High-resolution crystal structure determination of mTOR.
Analysis of structural elements including the FRB, LST8 binding element, and FATC domain.
Investigating the interaction of mTOR with rapamycin.

Main Results:

mTOR shares architectural principles with other PIKKs but possesses unique features for substrate specificity.
The FRB domain, LST8 binding element, and FATC domain contribute to mTOR's unique structure.
A conserved element in the FRB suggests a bipartite substrate recognition mechanism common to PIKKs.
Rapamycin acts as a competitive inhibitor of protein substrates by binding to the FRB domain.

Conclusions:

mTOR's unique structural elements, particularly the FRB domain, dictate its substrate specificity.
The bipartite substrate-binding site explains how rapamycin achieves substrate-specific inhibition.
Structural insights into mTOR can inform understanding of the broader PIKK family.