Publication Date:
2014-06-12
Description:
Ligation of tRNAs with their cognate amino acids, by aminoacyl-tRNA synthetases, establishes the genetic code. Throughout evolution, tRNA(Ala) selection by alanyl-tRNA synthetase (AlaRS) has depended predominantly on a single wobble base pair in the acceptor stem, G3*U70, mainly on the kcat level. Here we report the crystal structures of an archaeal AlaRS in complex with tRNA(Ala) with G3*U70 and its A3*U70 variant. AlaRS interacts with both the minor- and the major-groove sides of G3*U70, widening the major groove. The geometry difference between G3*U70 and A3*U70 is transmitted along the acceptor stem to the 3'-CCA region. Thus, the 3'-CCA region of tRNA(Ala) with G3*U70 is oriented to the reactive route that reaches the active site, whereas that of the A3*U70 variant is folded back into the non-reactive route. This novel mechanism enables the single wobble pair to dominantly determine the specificity of tRNA selection, by an approximate 100-fold difference in kcat.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4323281/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4323281/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Naganuma, Masahiro -- Sekine, Shun-ichi -- Chong, Yeeting Esther -- Guo, Min -- Yang, Xiang-Lei -- Gamper, Howard -- Hou, Ya-Ming -- Schimmel, Paul -- Yokoyama, Shigeyuki -- GM015539/GM/NIGMS NIH HHS/ -- GM023562/GM/NIGMS NIH HHS/ -- NS085092/NS/NINDS NIH HHS/ -- R01 GM015539/GM/NIGMS NIH HHS/ -- R01 GM023562/GM/NIGMS NIH HHS/ -- R01 GM100136/GM/NIGMS NIH HHS/ -- R01 NS085092/NS/NINDS NIH HHS/ -- England -- Nature. 2014 Jun 26;510(7506):507-11. doi: 10.1038/nature13440. Epub 2014 Jun 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] RIKEN Systems and Structural Biology Center, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan [2] Department of Biophysics and Biochemistry and Laboratory of Structural Biology, Graduate School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan [3] RIKEN Structural Biology Laboratory, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan. ; 1] RIKEN Systems and Structural Biology Center, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan [2] Department of Biophysics and Biochemistry and Laboratory of Structural Biology, Graduate School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan [3] Division of Structural and Synthetic Biology, RIKEN Center for Life Science Technologies, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan. ; 1] The Skaggs Institute for Chemical Biology and the Department of Cell and Molecular Biology, The Scripps Research Institute, BCC-379, 10550 North Torrey Pines Road, La Jolla, California 92037, USA [2] aTyr Pharma, 3545 John Hopkins Court, San Diego, California 92121, USA (Y.E.C.); Department of Cancer Biology, The Scripps Research Institute, 130 Scripps Way, Jupiter, Florida 33458, USA (M.G.). ; The Skaggs Institute for Chemical Biology and the Department of Cell and Molecular Biology, The Scripps Research Institute, BCC-379, 10550 North Torrey Pines Road, La Jolla, California 92037, USA. ; Department of Biochemistry and Molecular Biology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA. ; 1] The Skaggs Institute for Chemical Biology and the Department of Cell and Molecular Biology, The Scripps Research Institute, BCC-379, 10550 North Torrey Pines Road, La Jolla, California 92037, USA [2] The Scripps Florida Research Institute, 130 Scripps Way, 3B3 Jupiter, Florida 33458-5284, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24919148" target="_blank"〉PubMed〈/a〉
Keywords:
Adenosine Monophosphate/analogs & derivatives/chemistry
;
Alanine-tRNA Ligase/*chemistry
;
Archaeoglobus fulgidus/*enzymology/*genetics
;
*Base Pairing
;
Base Sequence
;
Catalytic Domain
;
Crystallography, X-Ray
;
Kinetics
;
Models, Molecular
;
RNA, Transfer, Ala/*chemistry/*genetics
;
Substrate Specificity
;
*Transfer RNA Aminoacylation
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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