Williams Sunanda Margrett, Chandran Anu Vijayakumari, Prakash Sunita, Vijayan Mamannamana, Chatterji Dipankar
Molecular Biophysics Unit, Indian Institute of Science, Bangalore 560 012, India.
Molecular Biophysics Unit, Indian Institute of Science, Bangalore 560 012, India.
Structure. 2017 Sep 5;25(9):1449-1454.e3. doi: 10.1016/j.str.2017.07.006. Epub 2017 Aug 17.
Proteins of the ferritin family are ubiquitous in living organisms. With their spherical cage-like structures they are the iron storehouses in cells. Subfamilies of ferritins include 24-meric ferritins and bacterioferritins (maxiferritins), and 12-meric Dps (miniferritins). Dps safeguards DNA by direct binding, affording physical protection and safeguards from free radical-mediated damage by sequestering iron in its core. The maxiferritins can oxidize and store iron but cannot bind DNA. Here we show that a mutation at a critical interface in Dps alters its assembly from the canonical 12-mer to a ferritin-like 24-mer under crystallization. This structural switch was attributed to the conformational alteration of a highly conserved helical loop and rearrangement of the C-terminus. Our results demonstrate a novel concept of mutational switch between related protein subfamilies and corroborate the popular model for evolution by which subtle substitutions in an amino acid sequence lead to diversification among proteins.
铁蛋白家族的蛋白质在生物体内普遍存在。它们具有球形笼状结构，是细胞中的铁储存库。铁蛋白的亚家族包括24聚体铁蛋白和细菌铁蛋白（最大铁蛋白），以及12聚体Dps（最小铁蛋白）。Dps通过直接结合来保护DNA，通过在其核心中螯合铁提供物理保护并防止自由基介导的损伤。最大铁蛋白可以氧化和储存铁，但不能结合DNA。在这里，我们表明，Dps中一个关键界面的突变在结晶过程中改变了其组装，从典型的12聚体转变为铁蛋白样的24聚体。这种结构转换归因于高度保守的螺旋环的构象改变和C末端的重排。我们的结果证明了相关蛋白质亚家族之间突变开关的新概念，并证实了流行的进化模型，即氨基酸序列中的细微取代导致蛋白质之间的多样化。
