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环二肽合酶与氨酰化 tRNA 底物相互作用的结构基础。

Structural basis of the interaction between cyclodipeptide synthases and aminoacylated tRNA substrates.

机构信息

Laboratoire de Biologie Structurale de la Cellule, BIOC, Ecole polytechnique, CNRS, Institut Polytechnique de Paris, 91128 Palaiseau cedex, France.

Université Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC), 91198, Gif-sur-Yvette, France.

出版信息

RNA. 2020 Nov;26(11):1589-1602. doi: 10.1261/rna.075184.120. Epub 2020 Jul 17.

DOI:10.1261/rna.075184.120
PMID:32680846
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7566563/
Abstract

Cyclodipeptide synthases (CDPSs) catalyze the synthesis of various cyclodipeptides by using two aminoacyl-tRNA (aa-tRNA) substrates in a sequential mechanism. Here, we studied binding of phenylalanyl-tRNA to the CDPS from (-CDPS) by gel filtration and electrophoretic mobility shift assay. We determined the crystal structure of the -CDPS:Phe-tRNA complex to 5 Å resolution and further studied it in solution using small-angle X-ray scattering (SAXS). The data show that the major groove of the acceptor stem of the aa-tRNA interacts with the enzyme through the basic β2 and β7 strands of CDPSs belonging to the XYP subfamily. A bending of the CCA extremity enables the amino acid moiety to be positioned in the P1 pocket while the terminal A76 adenosine occupies the P2 pocket. Such a positioning indicates that the present structure illustrates the binding of the first aa-tRNA. In cells, CDPSs and the elongation factor EF-Tu share aminoacylated tRNAs as substrates. The present study shows that CDPSs and EF-Tu interact with opposite sides of tRNA. This may explain how CDPSs hijack aa-tRNAs from canonical ribosomal protein synthesis.

摘要

环二肽合酶（CDPS）通过使用两种氨酰基-tRNA（aa-tRNA）底物以连续机制催化各种环二肽的合成。在这里，我们通过凝胶过滤和电泳迁移率变动分析研究了苯丙氨酰-tRNA与来自 (-CDPS)的 CDPS 的结合。我们确定了 -CDPS：Phe-tRNA 复合物的晶体结构，分辨率为 5 Å，并进一步使用小角度 X 射线散射（SAXS）在溶液中研究了它。数据表明，aa-tRNA 的接受茎的主沟通过属于 XYP 亚家族的 CDPSs 的碱性 β2 和 β7 链与酶相互作用。CCA 末端的弯曲使氨基酸部分能够定位在 P1 口袋中，而末端 A76 腺苷占据 P2 口袋。这种定位表明，目前的结构说明了第一个 aa-tRNA 的结合。在细胞中，CDPS 和延伸因子 EF-Tu 共享氨酰化的 tRNA 作为底物。本研究表明，CDPS 和 EF-Tu 与 tRNA 的相反侧相互作用。这可以解释 CDPS 如何从典型的核糖体蛋白合成中劫持 aa-tRNA。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5075/7566563/5a5416e75580/1589f07.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5075/7566563/dfee8c0462dc/1589f01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5075/7566563/46576619c08f/1589f02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5075/7566563/f3c5defcfbd6/1589f03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5075/7566563/863e979d83db/1589f04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5075/7566563/868daff07843/1589f05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5075/7566563/b688e6eab7f3/1589f06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5075/7566563/5a5416e75580/1589f07.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5075/7566563/dfee8c0462dc/1589f01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5075/7566563/46576619c08f/1589f02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5075/7566563/f3c5defcfbd6/1589f03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5075/7566563/863e979d83db/1589f04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5075/7566563/868daff07843/1589f05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5075/7566563/b688e6eab7f3/1589f06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5075/7566563/5a5416e75580/1589f07.jpg

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