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pH‐sensitive residues in the p19 RNA silencing suppressor protein from carnation Italian ringspot virus affect siRNA binding stability
dc.contributor.authorLaw, Sean M.en_US
dc.contributor.authorZhang, Bin W.en_US
dc.contributor.authorBrooks, Charles L.en_US
dc.date.accessioned2013-05-02T19:35:26Z
dc.date.available2014-07-01T15:53:37Zen_US
dc.date.issued2013-05en_US
dc.identifier.citationLaw, Sean M.; Zhang, Bin W.; Brooks, Charles L. (2013). "pH‐sensitive residues in the p19 RNA silencing suppressor protein from carnation Italian ringspot virus affect siRNA binding stability." Protein Science 22(5): 595-604. <http://hdl.handle.net/2027.42/97527>en_US
dc.identifier.issn0961-8368en_US
dc.identifier.issn1469-896Xen_US
dc.identifier.urihttps://hdl.handle.net/2027.42/97527
dc.description.abstractTombusviruses , such as Carnation Italian ringspot virus (CIRV), encode a protein homodimer called p19 that is capable of suppressing RNA silencing in their infected hosts by binding to and sequestering short‐interfering RNA (siRNA) away from the RNA silencing pathway. P19 binding stability has been shown to be sensitive to changes in pH but the specific amino acid residues involved have remained unclear. Using constant pH molecular dynamics simulations, we have identified key pH‐dependent residues that affect CIRV p19–siRNA binding stability at various pH ranges based on calculated changes in the free energy contribution from each titratable residue. At high pH, the deprotonation of Lys60, Lys67, Lys71, and Cys134 has the largest effect on the binding stability. Similarly, deprotonation of several acidic residues (Asp9, Glu12, Asp20, Glu35, and/or Glu41) at low pH results in a decrease in binding stability. At neutral pH, residues Glu17 and His132 provide a small increase in the binding stability and we find that the optimal pH range for siRNA binding is between 7.0 and 10.0. Overall, our findings further inform recent experiments and are in excellent agreement with data on the pH‐dependent binding profile.en_US
dc.publisherWiley Subscription Services, Inc., A Wiley Companyen_US
dc.subject.otherPH‐Dependenceen_US
dc.subject.otherCIRV P19en_US
dc.subject.otherConstant PH Molecular Dynamics Simulationsen_US
dc.subject.otherProtein–RNA Interactionsen_US
dc.titlepH‐sensitive residues in the p19 RNA silencing suppressor protein from carnation Italian ringspot virus affect siRNA binding stabilityen_US
dc.typeArticleen_US
dc.rights.robotsIndexNoFollowen_US
dc.subject.hlbsecondlevelBiological Chemistryen_US
dc.subject.hlbtoplevelHealth Sciencesen_US
dc.description.peerreviewedPeer Revieweden_US
dc.contributor.affiliationumDepartment of Chemistry and Biophysics Program, University of Michigan, Ann Arbor, MI 48109en_US
dc.contributor.affiliationumDepartment of Chemistry and Biophysics Program, University of Michigan, Ann Arbor, Michigan 48109en_US
dc.identifier.pmid23450521en_US
dc.description.bitstreamurlhttp://deepblue.lib.umich.edu/bitstream/2027.42/97527/1/2243_ftp.pdf
dc.description.bitstreamurlhttp://deepblue.lib.umich.edu/bitstream/2027.42/97527/2/PRO_2243_sm_SuppInfo.pdf
dc.identifier.doi10.1002/pro.2243en_US
dc.identifier.sourceProtein Scienceen_US
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dc.owningcollnameInterdisciplinary and Peer-Reviewed


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