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Side Chain IndependentRecognition of Aminoacyl Adenylates by the Hint1 Transcription Suppressor.
- Source :
-
Journal of Physical Chemistry B . Jun2012, Vol. 116 Issue 23, p6798-6805. 8p. - Publication Year :
- 2012
-
Abstract
- Human Hint1 suppresses specific gene transcription byinteracting with the transcription factor MITF in mast cells. Hint1activity is connected to lysyl-tRNA synthetase (LysRS), a member ofthe universal aminoacyl tRNA synthetase family that catalyzes specificaminoacylation of their cognate tRNAs, through an aminoacyl adenylate(aa-AMP) intermediate. During immune activation, LysRS produces aside-product diadenosine tetraphosphate (Ap4A) from thecondensation of Lys-AMP with ATP. The pleiotropic signaling moleculeAp4A then binds Hint1 to promote activation of MITF-targetgene transcription. Earlier work showed that Hint1 can also bind andhydrolyze Lys-AMP, possibly to constrain Ap4A production.Because Ap4A can result from condensation of other aa-AMP'swith ATP, the specificity of the Hint1 aa-AMPâhydrolysis activityis of interest. Here we show that Hint1 has broad specificity foradenylate hydrolysis, whose structural basis we revealed through high-resolutionstructures of Hint1 in complex with three different aa-AMP analogues.Hint1 recognizes only the common main chain of the aminoacyl moiety,and has no contact with the aa side chain. The α-amino groupis anchored by a cation-pi interaction with Trp123 at the C-terminusof Hint1. These results reveal the structural basis for the remarkableadenylate surveillance activity of Hint1, to potentially control Ap4A levels in the cell. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 15206106
- Volume :
- 116
- Issue :
- 23
- Database :
- Academic Search Index
- Journal :
- Journal of Physical Chemistry B
- Publication Type :
- Academic Journal
- Accession number :
- 80744042
- Full Text :
- https://doi.org/10.1021/jp212457w