Mechanism of Filamentation-Induced Allosteric Activation of the SgrAI Endonuclease
AffiliationUniv Arizona, Dept Mol & Cellular Biol
DNA sequence specificity
MetadataShow full item record
CitationPolley, S., Lyumkis, D., & Horton, N. C. (2019). Mechanism of filamentation-induced allosteric activation of the SgrAI endonuclease. Structure, 27(10), 1497-1507.
RightsCopyright © 2019 Elsevier Ltd.
Collection InformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at email@example.com.
AbstractFilament formation by enzymes is increasingly recognized as an important phenomenon with potentially unique regulatory properties and biological roles. SgrAI is an allosterically regulated type II restriction endonuclease that forms filaments with enhanced DNA cleavage activity and altered sequence specificity. Here, we present the cryoelectron microscopy (cryo-EM) structure of the filament of SgrAI in its activated configuration. The structural data illuminate the mechanistic origin of hyperaccelerated DNA cleavage activity and suggests how indirect DNA sequence readout within filamentous SgrAI may enable recognition of substantially more nucleotide sequences than its low-activity form, thereby altering and partially relaxing its DNA sequence specificity. Together, substrate DNA binding, indirect readout, and filamentation simultaneously enhance SgrAI's catalytic activity and modulate substrate preference. This unusual enzyme mechanism may have evolved to perform the specialized functions of bacterial innate immunity in rapid defense against invading phage DNA without causing damage to the host DNA.
Note12 month embargo; published online: 1 October 2019
VersionFinal accepted manuscript
SponsorsUnited States Department of Health & Human Services, National Institutes of Health (NIH) - USA [P41 GM103311]; National Science Foundation (NSF) [MCB-1410355]; United States Department of Health & Human Services, National Institutes of Health (NIH) - USA [DP5 OD021396]; DBT Wellcome Trust India Alliance [IA/I/15/1/501852]