核糖体是细胞内合成蛋白质的场所，是天然抗生素的主要靶标。德国Joerg M. Harms教授等人发现，含硫多肽类抗生素硫链丝菌肽（Thio）和微球菌素（Micro）通过L11这一分子开关控制核糖体的翻译过程，该研究结果发表在2008年4月11日的《分子细胞》（Molecular Cell）中。
含硫多肽类抗生素能够作用于核糖体的GTP酶相关位点，同时结合其中的蛋白质L11和rRNA。以往研究表明，其中的Thio和Micro通过该途径影响延伸因子EF-G的活性，通常认为Micro能够激活的GTP酶活性，而Thio则抑制这一过程，两者作用相反，Harms等人对此进行了深入研究。
使用X射线晶体衍射技术，研究人员确定了Thio和Micro与耐辐射菌（Deinococcus radiodurans）的核糖体大亚基的结合位点和作用方式。核糖体蛋白L11和23SrRNA的43/44螺旋结构形成裂隙，L11的构象变化能够加宽该裂隙从而允许延伸因子EF-G插入，促使GTP水解，为肽链延伸合成过程中核糖体的构象变化提供能量，而Thio能够与L11和23sRNA结合，阻止L11的构象变化，使该裂隙处于闭合状态，抑制EF－G在延伸过程中的作用。Micro与L11的结合能够促进其N末端结构域的构象发生变化，使其与核糖体蛋白L7结合，介导L7的C末端结构域与EF-G发生相互作用，促进GTP水解后Pi的释放。
由此可见，L11通过构象变化控制核糖体中蛋白质合成过程。所有生物体内均存在L11，并且其结构相当保守，表明这一分子开关的作用可能广泛存在。（科学网 穆宏平/编译）
生物谷推荐原始出处：
（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.
