Document Detail


Peripheral insertion modulates the editing activity of the isolated CP1 domain of leucyl-tRNA synthetase.
MedLine Citation:
PMID:  21819379     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
A large insertion domain called CP1 (connective peptide 1) present in class Ia aminoacyl-tRNA synthetases is responsible for post-transfer editing. LeuRS (leucyl-tRNA synthetase) from Aquifex aeolicus and Giardia lamblia possess unique 20 and 59 amino acid insertions respectively within the CP1 that are crucial for editing activity. Crystal structures of AaLeuRS-CP1 [2.4 Å (1 Å=0.1 nm)], GlLeuRS-CP1 (2.6 Å) and the insertion deletion mutant AaLeuRS-CP1Δ20 (2.5 Å) were solved to understand the role of these insertions in editing. Both insertions are folded as peripheral motifs located on the opposite side of the proteins from the active-site entrance in the CP1 domain. Docking modelling and site-directed mutagenesis showed that the insertions do not interact with the substrates. Results of molecular dynamics simulations show that the intact CP1 is more dynamic than its mutant devoid of the insertion motif. Taken together, the data show that a peripheral insertion without a substrate-binding site or major structural role in the active site may modulate catalytic function of a protein, probably from protein dynamics regulation in two respective LeuRS CP1s. Further results from proline and glycine mutational analyses intended to reduce or increase protein flexibility are consistent with this hypothesis.
Authors:
Ru-Juan Liu; Min Tan; Dao-Hai Du; Bei-Si Xu; Gilbert Eriani; En-Duo Wang
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Biochemical journal     Volume:  440     ISSN:  1470-8728     ISO Abbreviation:  Biochem. J.     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2011-11-14     Completed Date:  2012-01-05     Revised Date:  2012-07-27    
Medline Journal Info:
Nlm Unique ID:  2984726R     Medline TA:  Biochem J     Country:  England    
Other Details:
Languages:  eng     Pagination:  217-27     Citation Subset:  IM    
Affiliation:
State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, The Chinese Academy of Sciences, Shanghai 200031, People's Republic of China.
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MeSH Terms
Descriptor/Qualifier:
Bacteria / enzymology
Catalytic Domain / genetics
Crystallization
Giardia lamblia / enzymology
Leucine-tRNA Ligase / chemistry*,  genetics,  metabolism
Molecular Dynamics Simulation
Mutagenesis, Insertional
Protein Structure, Tertiary
RNA Editing*
RNA, Transfer, Amino Acyl / metabolism
Chemical
Reg. No./Substance:
0/RNA, Transfer, Amino Acyl; EC 6.1.1.4/Leucine-tRNA Ligase

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