Functional Evolution of Ribonuclease Inhibitor: Insights from Birds and Reptiles

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dc.citation.firstpage3041en_US
dc.citation.issueNumber17en_US
dc.citation.journalTitleJournal of Molecular Biologyen_US
dc.citation.lastpage3056en_US
dc.citation.volumeNumber426en_US
dc.contributor.authorLomax, Jo E.en_US
dc.contributor.authorBianchetti, Christopher M.en_US
dc.contributor.authorChang, Aramen_US
dc.contributor.authorPhillips, George N.Jr.en_US
dc.contributor.authorFox, Brian G.en_US
dc.contributor.authorRaines, Ronald T.en_US
dc.date.accessioned2015-03-16T16:56:10Zen_US
dc.date.available2015-03-16T16:56:10Zen_US
dc.date.issued2014en_US
dc.description.abstractRibonuclease inhibitor (RI) is a conserved protein of the mammalian cytosol. RI binds with high affinity to diverse secretory ribonucleases (RNases) and inhibits their enzymatic activity. Although secretory RNases are found in all vertebrates, the existence of a non-mammalian RI has been uncertain. Here, we report on the identification and characterization of RI homologs from chicken and anole lizard. These proteins bind to RNases from multiple species but exhibit much greater affinity for their cognate RNases than for mammalian RNases. To reveal the basis for this differential affinity, we determined the crystal structure of mouse, bovine, and chicken RI·RNase complexes to a resolution of 2.20, 2.21, and 1.92 Å, respectively. A combination of structural, computational, and bioinformatic analyses enabled the identification of two residues that appear to contribute to the differential affinity for RNases. We also found marked differences in oxidative instability between mammalian and non-mammalian RIs, indicating evolution toward greater oxygen sensitivity in RIs from mammalian species. Taken together, our results illuminate the structural and functional evolution of RI, along with its dynamic role in vertebrate biology.en_US
dc.identifier.citationLomax, Jo E., Bianchetti, Christopher M., Chang, Aram, et al.. "Functional Evolution of Ribonuclease Inhibitor: Insights from Birds and Reptiles." <i>Journal of Molecular Biology,</i> 426, no. 17 (2014) Elsevier: 3041-3056. http://dx.doi.org/10.1016/j.jmb.2014.06.007.en_US
dc.identifier.doihttp://dx.doi.org/10.1016/j.jmb.2014.06.007en_US
dc.identifier.urihttps://hdl.handle.net/1911/79354en_US
dc.language.isoengen_US
dc.publisherElsevieren_US
dc.rightsThis is an author's peer-reviewed final manuscript, as accepted by the publisher. The published article is copyrighted by Elsevier.en_US
dc.subject.keywordleucine-rich repeat (LRR)en_US
dc.subject.keywordprotein-protein interactionen_US
dc.subject.keywordreactive oxygen species (ROS)en_US
dc.subject.keywordredox homeostasisen_US
dc.subject.keywordribonucleaseen_US
dc.titleFunctional Evolution of Ribonuclease Inhibitor: Insights from Birds and Reptilesen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpost-printen_US
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