5DJ4

Leucine-bound Sestrin2 from Homo sapiens

Summary for 5DJ4

• Entry DOI: 10.2210/pdb5dj4/pdb
• Descriptor: Sestrin-2, LEUCINE (3 entities in total)
• Functional Keywords: mtor, leucine, amino-acid, sensing, signaling protein
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 5
• Total formula weight: 273458.70

Authors

Saxton, R.A.,Knockenhauer, K.E.,Schwartz, T.U. (deposition date: 2015-09-01, release date: 2015-11-25, Last modification date: 2024-03-06)

Primary citation

Saxton, R.A.,Knockenhauer, K.E.,Wolfson, R.L.,Chantranupong, L.,Pacold, M.E.,Wang, T.,Schwartz, T.U.,Sabatini, D.M.
Structural basis for leucine sensing by the Sestrin2-mTORC1 pathway.
Science, 351:53-58, 2016

PubMed Abstract: Eukaryotic cells coordinate growth with the availability of nutrients through the mechanistic target of rapamycin complex 1 (mTORC1), a master growth regulator. Leucine is of particular importance and activates mTORC1 via the Rag guanosine triphosphatases and their regulators GATOR1 and GATOR2. Sestrin2 interacts with GATOR2 and is a leucine sensor. Here we present the 2.7 angstrom 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.

PubMed: 26586190
DOI: 10.1126/science.aad2087

Experimental method

X-RAY DIFFRACTION (2.697 Å)