Sestrin 2

A leucine sensor and regulator of mTORC1 and protein synthesis

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I. Introduction

This is the structure of Sestrin 2 in complex with it ligand, the amino acid leucine. Sestrin 2 acts as a Leu sensor. This cause the dissociation of sestrin2:Leu from a protein called GATOR2 (GTPase-activating protein - GAP - activity toward Rags 2 (GATOR2). GATOR2 is yet another regulatory protein that activates mTORC1 by proteins called Rag proteins. Once dissociated GATOR blocks downstream inhibitors of mTORC1.

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

II. General Structure

Wireframe
cartoon
Bound Leu ligand
Spacefill showing bound Leu sequestered. Look for the yellow Leu and 3 amino acids (T374, T377, and T386) in red, which make a lid over the ligand

Leu is bound tightly and is mostly buried, suggesting a conformation change occurs after binding. The resiudes involved in binding surround the Leu, with T374, T377, and T386 acting as a lid, Y375 and H86 acting as a latch, and the nonpolar residiues F447 and W444 acting as a floor.

Lid (Thr374, Thr377, and Thr386) - wireframe; Latch (Tyr375 and His86) - blue wireframe; Floor (F447 and W444) - yellow wireframe