Yiting Yu, Lei Li, Sakharkar Meena Kishore, Kangueane Pandjassarame
School of Mechanical and Aerospace Engineering, Nanyang Technological University, 50, Nanyang Avenue, Singapore 639798.
Bioinformation. 2006 Feb 28;1(3):99-104. doi: 10.6026/97320630001099.
Gene fusion produces proteins with novel structural architectures during evolution. Recent comparative genome analysis shows several cases of fusion/fission across distant phylogeny. However, the selection forces driving gene fusion are not fully understood due to the lack of structural, dynamics and kinetics data. Available structural data at PDB (protein databank) contains limited cases of structural pairs describing fused and un-fused structures. Nonetheless, we identified a pair of IGPS (imidazole glycerol phosphate synthetase) structures (comprising of HisF - glutaminase unit and HisH - cyclase unit) from S. cerevisiae (SC) and T. thermophilus (TT). The HisF-HisH structural units are domains in SC and subunits in TT. Hence, they are fused in SC and un-fused in TT. Subsequently, a domain-domain interface is formed in SC and a subunit-subunit interface in TT between HisF and HisH. Our interest is to document the structure and dynamics differences between fused and un-fused IGPS. Therefore, we probed into the structures of fused IGPS in SC and un-fused IGPS in TT using molecular dynamics simulation for 5ns. Simulation shows that fused IGPS in SC has larger interface area between HisF-HisH and greater radius of gyration compared to un-fused IGPS in TT. These structural features for the first time demonstrate the evolutionary advantage in generating proteins with novel structural architecture through gene fusion.
基因融合在进化过程中产生具有新型结构架构的蛋白质。最近的比较基因组分析显示了跨远距离系统发育的几例融合/裂变情况。然而，由于缺乏结构、动力学和动力学数据，驱动基因融合的选择力尚未完全了解。蛋白质数据库（PDB）中现有的结构数据包含描述融合和未融合结构的结构对的有限案例。尽管如此，我们从酿酒酵母（SC）和嗜热栖热菌（TT）中鉴定出一对咪唑甘油磷酸合酶（IGPS）结构（由HisF-谷氨酰胺酶单元和HisH-环化酶单元组成）。HisF-HisH结构单元在SC中是结构域，在TT中是亚基。因此，它们在SC中融合而在TT中未融合。随后，在SC中HisF和HisH之间形成了结构域-结构域界面，在TT中形成了亚基-亚基界面。我们的兴趣在于记录融合和未融合的IGPS之间的结构和动力学差异。因此，我们使用5纳秒的分子动力学模拟探究了SC中融合的IGPS和TT中未融合的IGPS的结构。模拟表明，与TT中未融合的IGPS相比，SC中融合的IGPS在HisF-HisH之间具有更大的界面面积和更大的回转半径。这些结构特征首次证明了通过基因融合产生具有新型结构架构的蛋白质的进化优势。
