6KR7

Crystal structure of methylated human leucyl-tRNA synthetase, Leu-AMS-bound form

Summary for 6KR7

• Entry DOI: 10.2210/pdb6kr7/pdb
• Related: 6KIE
• Descriptor: Leucine--tRNA ligase, cytoplasmic, LEUCINE, 5'-O-(L-leucylsulfamoyl)adenosine, ... (5 entities in total)
• Functional Keywords: leucyl-trna synthetase, leu-ams-bound structure, ligase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 136740.98

Authors

Kim, S.,Son, J.,Kim, S.,Hwang, K.Y. (deposition date: 2019-08-21, release date: 2021-01-27, Last modification date: 2023-11-22)

Primary citation

Kim, S.,Yoon, I.,Son, J.,Park, J.,Kim, K.,Lee, J.H.,Park, S.Y.,Kang, B.S.,Han, J.M.,Hwang, K.Y.,Kim, S.
Leucine-sensing mechanism of leucyl-tRNA synthetase 1 for mTORC1 activation.
Cell Rep, 35:109031-109031, 2021

PubMed Abstract: Leucyl-tRNA synthetase 1 (LARS1) mediates activation of leucine-dependent mechanistic target of rapamycin complex 1 (mTORC1) as well as ligation of leucine to its cognate tRNAs, yet its mechanism of leucine sensing is poorly understood. Here we describe leucine binding-induced conformational changes of LARS1. We determine different crystal structures of LARS1 complexed with leucine, ATP, and a reaction intermediate analog, leucyl-sulfamoyl-adenylate (Leu-AMS), and find two distinct functional states of LARS1 for mTORC1 activation. Upon leucine binding to the synthetic site, H251 and R517 in the connective polypeptide and FPYPY in the catalytic domain change the hydrogen bond network, leading to conformational change in the C-terminal domain, correlating with RagD association. Leucine binding to LARS1 is increased in the presence of ATP, further augmenting leucine-dependent interaction of LARS1 and RagD. Thus, this work unveils the structural basis for leucine-dependent long-range communication between the catalytic and RagD-binding domains of LARS1 for mTORC1 activation.

PubMed: 33910001
DOI: 10.1016/j.celrep.2021.109031

Experimental method

X-RAY DIFFRACTION (4 Å)