近日，國際著名雜志Biochemical Journal 在線刊登了了上海生科院生化與細胞所王恩多課題組的最新研究成果“A naturally occurring nonapeptide functionally compensates the CP1 domain of leucyl-tRNA synthetase to modulate aminoacylation activity”,，文章中,，研究者在運動型支原體無編校結構域的LeuRS的催化機理獲得了進展。
氨基酰tRNA合成酶(aaRS)是蛋白質翻譯系統(tǒng)的重要組成部分,，其主要負責為蛋白質的生物合成提供原料：氨基酰-tRNA,。aaRS反應的精確性對正確翻譯遺傳信息致關重要。亮氨酰-tRNA合成酶（LeuRS）在進化過程中募集了插入合成氨基酰-tRNA活性中心的一個編校結構域（Connective peptide,， CP1）,，在該結構域內生成的錯誤氨基酰-tRNA被水解，從而保證催化反應的專一性,。目前已知的LeuRS中只有來自運動型支原體（Mycoplasma mobile）的LeuRS（MmLeuRS）無CP1,，而代之以含有九個氨基酸殘基的九肽（MmLinker）。
王恩多研究組的譚敏博士和博士研究生閆衛(wèi)等發(fā)現(xiàn),，MmLeuRS缺失了依賴tRNA的編校功能,；MmLinker對MmLeuRS的氨基酰化活力致關重要,，它可以功能性地代償其它物種LeuRS的CP1在氨基酰化反應中的作用,。來自大腸桿菌的LeuRS的CP1（EcCP1）可以在MmLeuRS中代替MmLinker發(fā)揮作用,，EcCP1融合進MmLeuRS可賦予MmLeuRS轉移后編?；盍砭S持催化反應的專一性。通過無CP1的MmLeuRS的研究發(fā)現(xiàn)：LeuRS的轉移前編?；盍κ窃诤铣砂被?tRNA的結構域進行的,。
該論文為aaRS的模塊融合進化假說提供了直接的證據(jù)，同時也為LeuRS轉移前編校的分子機制的研究提供了線索,。
該項研究工作得到了國家科技部,、國家基金委、中國科學院的資助,。（生物谷Bioon.com）
doi:10.1042/BJ20111925
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A naturally occurring nonapeptide functionally compensates the CP1 domain of leucyl-tRNA synthetase to modulate aminoacylation activity
Min Tan, Wei Yan, Ru-Juan Liu, Meng Wang, Xin Chen, Xiao-Long Zhou and En-Duo Wang
Aminoacyl-tRNA synthetases (aaRSs) establish the rules of the genetic code by catalyzing the formation of aminoacyl-tRNA. The quality control for aminoacylation reaction is achieved by editing activity, which is usually carried out by a discrete editing domain. For leucyl-tRNA synthetase (LeuRS), the connective peptide 1 (CP1) domain is the editing domain responsible for hydrolyzing mis-charged tRNA. The CP1 domain is universally present in LeuRSs except LeuRS from Mycoplasma mobile (MmLeuRS). The substitute of CP1 in MmLeuRS is a nonapeptide (MmLinker). We show here that the MmLinker, which is critical for aminoacylation activity of MmLeuRS, could confer remarkable tRNA charging activity to the inactive CP1-deleted LeuRS from Escherichia coli (EcLeuRS) and Aquifex aeolicus (AaLeuRS). Furthermore, CP1 from EcLeuRS could functionally compensate the MmLinker and endow MmLeuRS with post-transfer editing capability. These investigations provide a mechanistic framework for the modular construction of aaRSs and their coordination to achieve catalytic efficiency and fidelity. These results also show that the pre-transfer editing function of LeuRS originates from its conserved synthetic domain, and shed light on future mechanism study.
