核糖體是細(xì)胞內(nèi)合成蛋白質(zhì)的場所,，是天然抗生素的主要靶標(biāo),。德國Joerg M. Harms教授等人發(fā)現(xiàn)，含硫多肽類抗生素硫鏈絲菌肽（Thio）和微球菌素（Micro）通過L11這一分子開關(guān)控制核糖體的翻譯過程,，該研究結(jié)果發(fā)表在2008年4月11日的《分子細(xì)胞》（Molecular Cell）中,。
含硫多肽類抗生素能夠作用于核糖體的GTP酶相關(guān)位點,，同時結(jié)合其中的蛋白質(zhì)L11和rRNA。以往研究表明,，其中的Thio和Micro通過該途徑影響延伸因子EF-G的活性，通常認(rèn)為Micro能夠激活的GTP酶活性,，而Thio則抑制這一過程,，兩者作用相反，Harms等人對此進(jìn)行了深入研究,。
使用X射線晶體衍射技術(shù),，研究人員確定了Thio和Micro與耐輻射菌（Deinococcus radiodurans）的核糖體大亞基的結(jié)合位點和作用方式。核糖體蛋白L11和23SrRNA的43/44螺旋結(jié)構(gòu)形成裂隙,，L11的構(gòu)象變化能夠加寬該裂隙從而允許延伸因子EF-G插入,，促使GTP水解，為肽鏈延伸合成過程中核糖體的構(gòu)象變化提供能量,，而Thio能夠與L11和23sRNA結(jié)合,，阻止L11的構(gòu)象變化，使該裂隙處于閉合狀態(tài),，抑制EF－G在延伸過程中的作用,。Micro與L11的結(jié)合能夠促進(jìn)其N末端結(jié)構(gòu)域的構(gòu)象發(fā)生變化，使其與核糖體蛋白L7結(jié)合,，介導(dǎo)L7的C末端結(jié)構(gòu)域與EF-G發(fā)生相互作用,，促進(jìn)GTP水解后Pi的釋放。
由此可見,，L11通過構(gòu)象變化控制核糖體中蛋白質(zhì)合成過程,。所有生物體內(nèi)均存在L11，并且其結(jié)構(gòu)相當(dāng)保守,，表明這一分子開關(guān)的作用可能廣泛存在,。（科學(xué)網(wǎng) 穆宏平/編譯）
生物谷推薦原始出處：
（Molecular Cell），26-38, 11 April 2008,，Joerg M. Harms, Paola Fucini
Translational Regulation via L11: Molecular Switches on the Ribosome Turned On and Off by Thiostrepton and Micrococcin
Joerg M. Harms,1,2,8 Daniel N. Wilson,2,3,4,8, Frank Schluenzen,2,5,8 Sean R. Connell,1,6 Torsten Stachelhaus,7,9 Zaneta Zaborowska,1 Christian M.T. Spahn,6 and Paola Fucini1,2,
1 Cluster of Excellence for Macromolecular Complexes, Institut für Organische Chemie und Chemische Biologie, J.W. Goethe-Universität Frankfurt am Main, Max-von-Laue-Strasse 7, D-60438 Frankfurt am Main, Germany
2 Max-Planck-Institute for Molecular Genetics, AG-Ribosomen, Ihnestrasse 73, D-14195 Berlin, Germany
3 Gene Center and Department of Chemistry and Biochemistry, University of Munich, LMU, Feodor Lynen Strasse 25, 81377 Munich, Germany
4 Munich Centre for Integrated Protein Science, University of Munich, 81377 Munich, Germany
5 Deutsches Elektronen-Synchrotron, Notkestrasse 85, D-22603 Hamburg, Germany
6 Institut für Medizinische Physik und Biophysik, Charite—Universitätsmedizin Berlin, Ziegelstrasse 5-9, 10117 Berlin, Germany
7 Department of Chemistry/Biochemistry, Philipps University of Marburg, Hans-Meerwein-Strasse, D-35032 Marburg, Germany
Summary
The thiopeptide class of antibiotics targets the GTPase-associated center (GAC) of the ribosome to inhibit translation factor function. Using X-ray crystallography, we have determined the binding sites of thiostrepton (Thio), nosiheptide (Nosi), and micrococcin (Micro), on the Deinococcus radiodurans large ribosomal subunit. The thiopeptides, by binding within a cleft located between the ribosomal protein L11 and helices 43 and 44 of the 23S rRNA, overlap with the position of domain V of EF-G, thus explaining how this class of drugs perturbs translation factor binding to the ribosome. The presence of Micro leads to additional density for the C-terminal domain (CTD) of L7, adjacent to and interacting with L11. The results suggest that L11 acts as a molecular switch to control L7 binding and plays a pivotal role in positioning one L7-CTD monomer on the G′ subdomain of EF-G to regulate EF-G turnover during protein synthesis.
