Structures of replication initiation proteins from staphylococcal antibiotic resistance plasmids reveal protein asymmetry and flexibility are necessary for replication.
Structures of replication initiation proteins from staphylococcal antibiotic resistance plasmids reveal protein asymmetry and flexibility are necessary for replication.
复制标题
来自葡萄球菌抗生素耐药性质粒的复制起始蛋白的结构揭示了蛋白质不对称性，并且灵活性对于复制是必要的。
DOI：
10.1093/nar/gkv1539
复制
发表时间：
2016-03-18
影响因子：
14.9
通讯作者：
Thomas CD
中科院分区：
文献类型：
--
作者：
Carr SB;Phillips SE;Thomas CD
病原菌对抗生素的耐药性是对人类健康的持续威胁，通常存在于染色体外质粒DNA中。PT181家族的质粒广泛存在，对金黄色葡萄球菌具有多种抗药性。它们通过滚环机制进行复制，这需要一个多功能的、质粒编码的复制蛋白来启动复制，在起始位置招募解旋酶，并在DNA合成完成后终止复制。我们提出了三个这样的复制蛋白的第一个原子分辨结构，它们显示了不同的、功能相关的构象。这些蛋白质具有独特的活性部位，并已被证明含有一种催化必需的金属离子，其结合方式与任何其他滚环复制蛋白不同。这些结构是Rep_Trans Pfam家族的第一个例子，为从革兰氏阳性细菌复制大量抗生素耐药质粒、革兰氏阴性噬菌体以及通过接合转座子动员DNA提供了见解。
Antibiotic resistance in pathogenic bacteria is a continual threat to human health, often residing in extrachromosomal plasmid DNA. Plasmids of the pT181 family are widespread and confer various antibiotic resistances to Staphylococcus aureus. They replicate via a rolling circle mechanism that requires a multi-functional, plasmid-encoded replication protein to initiate replication, recruit a helicase to the site of initiation and terminate replication after DNA synthesis is complete. We present the first atomic resolution structures of three such replication proteins that reveal distinct, functionally relevant conformations. The proteins possess a unique active site and have been shown to contain a catalytically essential metal ion that is bound in a manner distinct from that of any other rolling circle replication proteins. These structures are the first examples of the Rep_trans Pfam family providing insights into the replication of numerous antibiotic resistance plasmids from Gram-positive bacteria, Gram-negative phage and the mobilisation of DNA by conjugative transposons.