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The Need for Speed: Run-On Oligomer Filament Formation Provides Maximum Speed with Maximum Sequestration of Activity

2018; American Society for Microbiology; Volume: 93; Issue: 5 Linguagem: Inglês

10.1128/jvi.01647-18

1098-5514

Claudia Barahona, L. Emilia Basantes, Kassidy J. Tompkins, Desirae M. Heitman, Barbara I. Chukwu, Juan C Sanchez, Jonathan L. Sanchez, Niloofar Ghadirian, Chad K. Park, Nancy C. Horton,

Virus-based gene therapy research

This work is motivated by an interest in understanding the characteristics and advantages of a relatively newly discovered enzyme mechanism involving filament formation. SgrAI is an enzyme responsible for protecting against viral infections in its host bacterium and was one of the first such enzymes shown to utilize such a mechanism. In this work, filament formation by SgrAI is disrupted, and the effects on the speed of the purified enzyme as well as its function in cells are measured. It was found that even small disruptions, which weaken but do not destroy filament formation, eliminate the ability of SgrAI to protect cells from viral infection, its normal biological function. Simulations of enzyme activity were also performed and show how filament formation can greatly speed up an enzyme’s activation compared to that of other known mechanisms, as well as to better localize its action to molecules of interest, such as invading phage DNA.