Table of Contents
Role of tRNA synthetases in Translation
tRNA synthetases, better known as aminoacyl
tRNA synthetases, play a major role in translation during protein synthesis.
Since a protein's structure and function depend absolutely on its primary
structure, or amino acid sequence, errors in protein synthesis have terrible
consequences. The translation of genetic information is mediated
by adaptor molecules, tRNAs, which recognize a triplet on the mRNA through
a complementarity region called an anticodon and carry a covalently attached
amino acid corresponding to that triplet in the genetic code (1).
Aminoacyl tRNA synthetases are the enzymes that are responsible for the
specific aminoacylation of tRNA. The selectivity in their recognition
of both the amino acid to be activated and the cognate tRNA is a crucial
step in the fidelity of the translation of the genetic code.
In order to have a better understanding of the role tRNA synthetases, it is important t understand the basic features of tRNA.
tRNa Structure - Cloverleaf Model
The anticodon triplet in the loop at the bottom is complementary to the mRNA codon and will make base pairs with it.
The acceptor stem at the top of the cloverleaf figure is where the aminoacid will be attached at the 3' terminus of the tRNA. This stem always has the sequence 5'...CCA-OH3'.
The D loop and the TyC loop contain a substantial fraction of invariant positions.
The variable loop is variable both in nucleotide composition
and in length (2).
Role of tRNA synthetases in Translation
The accuracy of protein translation depends on the fidelity with which the correct amino acids are esterified to their cognate tRNA molecules by aminoacyl tRNA synthetases. Despite the structural differences between Class I and Class II, all aminoacyl tRNA synthetases carry out the same two-step reaction (3,4).
In the first step, the enzyme binds ATP and the amino acid, and catalyzes the formation of an aminoacyl-adenylate intermediate, in which a covalent linkage is formed between the 5'-phosphate group of ATP and the carboxyl end of the amino acid (5,6). The aminoacyl tRNA synthetase uses the energy generated by ATP hydrolysis to activate the amino acid, forming the aminoacyl-AMP that remains associated with the enzyme.(7) The bonds between phosphate groups in ATP are high energy bonds. When they are broken, this energy is trapped in the aminoacyl-AMP, which is why we call this an activated amino acid.
In the second step, the amino acid is transferred to the appropriate tRNA and bonded covalently to either the 2'OH or 3'OH of the invariant 3' adenosine terminal of the tRNA molecule. The energy in the aminoacyl-AMP is used to transfer the amino acid to the tRNA forming amioacyl-tRNA.
When an amino acid binds to the
3'-end of a tRNA, we say the tRNA is charged with that amino acid.
The amino acid group and the hydroxyl group are linked together by an ester
Factors that determine the specificity of tRNA synthetases:
1.Onesti, Silvia; Gianluigi Desogus; Annie Brevet; Josiane Chen; Pierre Plateau; Sylvain Blanquet;
and Peter Brick. "Structural Studies on Lysyl-tRNA Synthetase: Conformational Changes Induced
by Substrate Binding." Biochemistry, 2000 vol 39 12852-12861.
K. E. van Holde; and Kevin Ahern. Biochemistry. 3rd
Edition. San Francisco:
Addison Wesley Longman, 2000.
3.Qiu, Xiayang; Cheryl Janson; Michael Blackburn; Inderjit
Chhohan; Martin Hibbs; and Sherin
Abdel-Meguid. "Cooperative Structural Dynamics and a Novel Fidelity Mechanism in Histidyl-tRNA
Synthetases." Biochemistry, vol 38, 12296-12304.
4.Weaver, Robert; and Philip Hedrick. Genetics. 3rd Edition. Dubuque, IA: WCB, 1997.
5.Desogus, Gianluigi; Flavia Todone; Peter Brick; and
Silvia Onesti. "Active Site of Lysyl-tRNA
Synthetase: Structural Sudies of the Adenylation Reaction. Biochemistry, 2000 vol 39, 8418-8425.
6. Klug, William, and
Concepts of Genetics.5th Edition. Upper
Saddle River, NJ:
Prentice Hall, 1997.
Leroy Hodd; Michael Goldberg; Ann Reynolds; Lee Silver; and Ruth Veres.
Genetics: From Genes to Genomes. Boston: Mgraw-Hill, 1999.
Atherly, Alan; Jack
Girton; and John McDonald. The Science of Genetics.
Austin: Saunders College
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