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dc.contributor.authorPolley, Smarajit
dc.contributor.authorLyumkis, Dmitry
dc.contributor.authorHorton, Nancy C
dc.date.accessioned2019-11-07T01:18:12Z
dc.date.available2019-11-07T01:18:12Z
dc.date.issued2019-10-01
dc.identifier.citationPolley, S., Lyumkis, D., & Horton, N. C. (2019). Mechanism of filamentation-induced allosteric activation of the SgrAI endonuclease. Structure, 27(10), 1497-1507.en_US
dc.identifier.issn0969-2126
dc.identifier.pmid31447289
dc.identifier.doi10.1016/j.str.2019.08.001
dc.identifier.urihttp://hdl.handle.net/10150/634970
dc.description.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.en_US
dc.description.sponsorshipUnited 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]en_US
dc.language.isoenen_US
dc.publisherCELL PRESSen_US
dc.rightsCopyright © 2019 Elsevier Ltd.en_US
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/
dc.subjectDNA bindingen_US
dc.subjectDNA sequence specificityen_US
dc.subjectallosteryen_US
dc.subjectcryo-EMen_US
dc.subjectendonucleaseen_US
dc.subjectenzyme mechanismen_US
dc.subjectfilament-forming enzymeen_US
dc.subjectindirect readouten_US
dc.subjectprotein filamenten_US
dc.subjectself-associationen_US
dc.titleMechanism of Filamentation-Induced Allosteric Activation of the SgrAI Endonucleaseen_US
dc.typeArticleen_US
dc.contributor.departmentUniv Arizona, Dept Mol & Cellular Biolen_US
dc.identifier.journalSTRUCTUREen_US
dc.description.note12 month embargo; published online: 1 October 2019en_US
dc.description.collectioninformationThis 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 repository@u.library.arizona.edu.en_US
dc.eprint.versionFinal accepted manuscripten_US
dc.source.journaltitleStructure (London, England : 1993)


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