Department of Biochemistry and Biomedical Sciences and M G DeGroote Institute for Infectious Disease Research, McMaster University, 1200 Main Street West, Hamilton, Ontario L8N 3Z5, Canada.
Nucleic Acids Res. 2010 Jun;38(10):3432-40. doi: 10.1093/nar/gkq036. Epub 2010 Feb 2.
Deinococcus spp. are renowned for their amazing ability to recover rapidly from severe genomic fragmentation as a result of exposure to extreme levels of ionizing radiation or desiccation. Despite having been originally characterized over 50 years ago, the mechanism underlying this remarkable repair process is still poorly understood. Here, we report the 2.8 A structure of DdrB, a single-stranded DNA (ssDNA) binding protein unique to Deinococcus spp. that is crucial for recovery following DNA damage. DdrB forms a pentameric ring capable of binding single-stranded but not double-stranded DNA. Unexpectedly, the crystal structure reveals that DdrB comprises a novel fold that is structurally and topologically distinct from all other single-stranded binding (SSB) proteins characterized to date. The need for a unique ssDNA binding function in response to severe damage, suggests a distinct role for DdrB which may encompass not only standard SSB protein function in protection of ssDNA, but also more specialized roles in protein recruitment or DNA architecture maintenance. Possible mechanisms of DdrB action in damage recovery are discussed.
耐辐射球菌属因其在暴露于极端水平的电离辐射或干燥时，能够迅速从严重的基因组碎片化中恢复的惊人能力而闻名。尽管它们在 50 多年前就已经被最初描述过，但这种非凡的修复过程的机制仍然知之甚少。在这里，我们报告了 DdrB 的 2.8A 结构，DdrB 是一种仅存在于耐辐射球菌属的单链 DNA（ssDNA）结合蛋白，对于 DNA 损伤后的恢复至关重要。DdrB 形成五聚体环，能够结合单链但不能结合双链 DNA。出乎意料的是，晶体结构表明 DdrB 包含一种新颖的折叠结构，在结构和拓扑上与迄今为止所有表征的其他单链结合（SSB）蛋白都不同。对严重损伤做出独特的 ssDNA 结合功能的需求表明，DdrB 可能具有独特的作用，不仅包括在保护 ssDNA 方面的标准 SSB 蛋白功能，还包括在蛋白质募集或 DNA 结构维持方面的更专门的作用。讨论了 DdrB 在损伤恢复中作用的可能机制。
