Novel mutations in ribosomal proteins L4 and L22 that confer erythromycin resistance in Escherichia coli.
Novel mutations in ribosomal proteins L4 and L22 that confer erythromycin resistance in Escherichia coli.
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DOI：
10.1111/j.1365-2958.2007.05975.x
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发表时间：
2007-11
影响因子：
3.6
通讯作者：
Zengel J
中科院分区：
文献类型：
--
作者：
Zaman S;Fitzpatrick M;Lindahl L;Zengel J
L4和L22是核糖体大亚基的蛋白质，含有球状表面结构域和细长的“触角”，它们伸入大亚基的核心，形成肽出口隧道衬里的一部分。L4和L22触手中的突变在多种致病性和非致病性细菌中赋予大环内酯抗性。在大肠杆菌中，L4中的Lys-to-Glu突变和L22中的三个氨基酸缺失已被报道。为了进一步了解触角在核糖体组装和功能中的作用，我们分离了另外一株红霉素耐药的E。coli突变体。在L4中定位了8个新的突变，都在tengland内。在L22中发现了两个新的突变;一个定位在肌腱外。两个基因均存在插入突变。所有突变体的生长速度都比亲本慢，并且它们都显示出体内肽链延长速率降低和前体23 S rRNA水平增加。L4和L22中的大插入导致非常缓慢的生长和异常核糖体亚基的积累。我们的研究结果突出了L4和L22在核糖体功能和组装中的重要作用，并表明这些蛋白质的各种变化可以介导大环内酯类药物耐药性。
L4 and L22, proteins of the large ribosomal subunit, contain globular surface domains and elongated ‘tentacles’ that reach into the core of the large subunit to form part of the lining of the peptide exit tunnel. Mutations in the tentacles of L4 and L22 confer macrolide resistance in a variety of pathogenic and non-pathogenic bacteria. In Escherichia coli, a Lys-to-Glu mutation in L4 and a three-amino-acid deletion in the L22 had been reported. To learn more about the roles of the tentacles in ribosome assembly and function, we isolated additional erythromycin-resistant E. coli mutants. Eight new mutations mapped in L4, all within the tentacle. Two new mutations were identified in L22; one mapped outside the tentacle. Insertion mutations were found in both genes. All of the mutants grew slower than the parent, and they all showed reduced in vivo rates of peptide-chain elongation and increased levels of precursor 23S rRNA. Large insertions in L4 and L22 resulted in very slow growth and accumulation of abnormal ribosomal subunits. Our results highlight the important role of L4 and L22 in ribosome function and assembly, and indicate that a variety of changes in these proteins can mediate macrolide resistance.
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DOI：
10.1073/pnas.0607541103
发表时间：
2006-10-24
影响因子：
11.1
作者：
Berk, Veysel;Zhang, Wen;Cate, Jamie H. Doudna
通讯作者：
Cate, Jamie H. Doudna
影响因子：
3.6
作者：
Hage, AE;Alix, JH
通讯作者：
Alix, JH
DOI：
10.1073/pnas.172404099
发表时间：
2002-09-03
影响因子：
11.1
作者：
Hansen, JL;Schmeing, TM;Steitz, TA
通讯作者：
Steitz, TA
影响因子：
4.9
作者：
MENNINGER, JR;OTTO, DP
通讯作者：
OTTO, DP
影响因子：
16
作者：
Gabashvili, IS;Gregory, ST;Frank, J
通讯作者：
Frank, J