mTOR Complex I  (mTORC1)

A master regulator of growth

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I. Introduction

mTORC1 is a complicated complex of many proteins.  The main kinase, mTOR, has a typical kinase structure with an N and C lobe.  However, it has insertions that help determine specificity.  These additions allow binding to other proteins which help regulate the specificity of the mTOR kinase.

 For more information see Biochemistry Online: Chapter 9D - Nutrient Signaling 

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II. General Structure

Wireframe
cartoon with bound rapamycin

The complex acts physiologically as a dimer with rotational C2 symmetry.

• mTOR kinase as homodimer - Red; Chains B,F ,1-4  
• Raptor - orange; Chains A and E
• LST8 - green; chains D and H
•  FKBP - blue; chains C and G 
• Rapamycin - yellow spacefill in chains C and G

They are described briefly below:

• mTOR, a Ser/Thr kinase;
• Raptor, a Regulatory-associated protein of mTOR;  it modulates the specificity of the kinase;  
• mLST8, the mammalian lethal with SEC13 protein 8 (also called Mammalian Lethal With SEC13 Protein 8

In addition, other proteins  associate with the core complex include:

• PRAS40, a proline-rich Akt substrate of Akt ;
• DEPTOR , DEP Domain Containing MTOR-Interacting Protein (where DEP is Dishevelled, Egl-10 and Pleckstrin domain found in these 3 proteins and others involved in G-protein signaling);
• FKBP, which binds rapamycin.

Raptor has been likened to tape as it interacts with the two mTOR subunits, holding them together into a larger, donut-like structure, stabilizing the dimer.