Interdomain compactization in human tyrosyl-tRNA synthetase studied by the hierarchical rotations technique
S O Yesylevskyy1, O V Savytskyi, K A Odynets
1Department of Physics of Biological Systems, Institute of Physics, National Academy of Sciences of Ukraine, Kiev, Ukraine. yesint3@yahoo.com
Biophysical Chemistry
|February 16, 2011
Summary
Human tyrosyl-tRNA synthetase, crucial for protein synthesis, has two main modules. This study used HIEROT to reveal potential binding interfaces between these modules, identifying key "hot spots" for further research.
Area of Science:
- Biochemistry
- Structural Biology
- Molecular Biology
Background:
- Aminoacyl-tRNA synthetases are essential enzymes for protein biosynthesis, typically featuring multidomain structures.
- Human cytoplasmic tyrosyl-tRNA synthetase consists of an N-terminal catalytic core and a C-terminal EMAPII-like domain, linked by a flexible region.
- The complete structure of full-length human cytoplasmic tyrosyl-tRNA synthetase remains undetermined, with debates on the compact arrangement of its resolved domains.
Purpose of the Study:
- To investigate the potential compactization of the N- and C-terminal modules of human tyrosyl-tRNA synthetase.
- To identify possible binding interfaces between these modules in the absence of substrates.
- To computationally predict residue-level binding propensities and identify key interaction sites.
Main Methods:
- Utilized the coarse-grained hierarchical rotations (HIEROT) technique.
- Analyzed the potential conformational states and inter-module interactions.
- Computed binding propensities for residues on both N- and C-terminal modules.
Main Results:
- Revealed a large number of distinct potential binding interfaces between the N- and C-terminal modules.
- Identified specific residues and regions as binding "hot spots" on both modules.
- Provided insights into the possible structural arrangements of the enzyme's domains.
Conclusions:
- The study elucidates potential inter-module interactions in human tyrosyl-tRNA synthetase.
- Identified binding "hot spots" can guide future experimental studies, including atomistic molecular dynamics simulations.
- These findings contribute to a better understanding of the enzyme's functional structure and regulation.
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