5dj4 | pdb_00005dj4

Leucine-bound Sestrin2 from Homo sapiens

spinqualitylabelsall models 5dj4, resolution 2.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5dj4 is a 5 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: LEU Gene: SESN2, SEST2 (HUMAN) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [SESN2_HUMAN] Involved in the reduction of peroxiredoxins. Publication Abstract from PubMed Eukaryotic cells coordinate growth with the availability of nutrients through mTOR complex 1 (mTORC1), a master growth regulator. Leucine is of particular importance and activates mTORC1 via the Rag GTPases and their regulators GATOR1 and GATOR2. Sestrin2 interacts with GATOR2 and is a leucine sensor. We present the 2.7-A crystal structure of Sestrin2 in complex with leucine. Leucine binds through a single pocket that coordinates its charged functional groups and confers specificity for the hydrophobic side chain. A loop encloses leucine and forms a lid-latch mechanism required for binding. A structure-guided mutation in Sestrin2 that decreases its affinity for leucine leads to a concomitant increase in the leucine concentration required for mTORC1 activation in cells. These results provide a structural mechanism of amino acid sensing by the mTORC1 pathway. Structural basis for leucine sensing by the Sestrin2-mTORC1 pathway.,Saxton RA, Knockenhauer KE, Wolfson RL, Chantranupong L, Pacold ME, Wang T, Schwartz TU, Sabatini DM Science. 2015 Nov 19. pii: aad2087. PMID:26586190 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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