2.8-Å Cryo-EM Structure of the Large Ribosomal Subunit from the Eukaryotic Parasite Leishmania.
2.8-Å Cryo-EM Structure of the Large Ribosomal Subunit from the Eukaryotic Parasite Leishmania.
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DOI：
10.1016/j.celrep.2016.06.014
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发表时间：
2016-07-12
期刊：
影响因子：
8.8
通讯作者：
Skiniotis G
中科院分区：
文献类型：
--
作者：
Shalev-Benami M;Zhang Y;Matzov D;Halfon Y;Zackay A;Rozenberg H;Zimmerman E;Bashan A;Jaffe CL;Yonath A;Skiniotis G
利什曼原虫是锥虫科的单细胞真核寄生虫，其成员引起一系列热带疾病。感染的结果往往是致命的，缺乏有效的疫苗，治疗药物的选择有限，以及新出现的耐药菌株，这些都突出表明需要制定防治这些病原体的战略。锥虫核糖体由于其不同于其他真核生物的结构特征，最近被强调为有希望的治疗靶点。在这里，我们提出了2.8-ε分辨率结构的杜氏利什曼原虫核糖体大亚基（LSU）来自冷冻电镜图，进一步使结构观察真核rRNA修饰，在核糖体组装和功能中发挥重要作用。该结构说明了利什曼原虫LSU rRNA独特的片段化性质，并突出了利什曼原虫rRNA修饰的不规则分布，这一特征对抗寄生虫发育具有重要意义。Shalev-Benami等人描述了杜氏利什曼原虫核糖体大亚基的结构，通过冷冻电镜以2.8-nm分辨率获得。该结构显示了利什曼原虫rRNA的片段化性质，并突出了rRNA修饰的不规则分布，这对药物开发具有影响，该原生动物寄生虫困扰着全世界数百万人。
Leishmania is a single cell eukaryotic parasite of the Trypanosomatidae family, whose members cause an array of tropical diseases. The often fatal outcome of infections, lack of effective vaccines, limited selection of therapeutic drugs and emerging resistant strains, underline the need to develop strategies to combat these pathogens. The Trypanosomatid ribosome has recently been highlighted as a promising therapeutic target, due to structural features that are distinct from other eukaryotes. Here we present the 2.8-Å resolution structure of the Leishmania donovani large ribosomal subunit (LSU) derived from a cryo-EM map, further enabling the structural observation of eukaryotic rRNA modifications that play a significant role in ribosome assembly and function. The structure illustrates the unique fragmented nature of leishmanial LSU rRNA and highlights the irregular distribution of rRNA modifications in Leishmania, a characteristic with implications for anti-parasitic development. Shalev-Benami et al. describe the structure of the Leishmania donovani large ribosomal subunit, obtained by cryo-EM at 2.8-Å resolution. The structure shows the fragmented nature of leishmanial rRNA and highlights the irregular distribution of rRNA modifications with implications for drug development against this protozoan parasite, which afflicts millions of people worldwide.
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影响因子：
10.5
作者：
Gamalinda M;Ohmayer U;Jakovljevic J;Kumcuoglu B;Woolford J;Mbom B;Lin L;Woolford JL Jr
通讯作者：
Woolford JL Jr
DOI：
10.1126/science.1208245
发表时间：
2011-09-09
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Strunk BS;Loucks CR;Su M;Vashisth H;Cheng S;Schilling J;Brooks CL 3rd;Karbstein K;Skiniotis G
通讯作者：
Skiniotis G
影响因子：
64.8
作者：
Brown A;Shao S;Murray J;Hegde RS;Ramakrishnan V
通讯作者：
Ramakrishnan V
DOI：
10.1073/pnas.0500926102
发表时间：
2005-07-19
影响因子：
11.1
作者：
Gao, HX;Ayub, MJ;Frank, J
通讯作者：
Frank, J
影响因子：
3
作者：
Scheres, Sjors H. W.
通讯作者：
Scheres, Sjors H. W.