Functional Evolution of Ribonuclease Inhibitor: Insights from Birds and Reptiles

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dc.citation.firstpage3041
dc.citation.issueNumber17
dc.citation.journalTitleJournal of Molecular Biology
dc.citation.lastpage3056
dc.citation.volumeNumber426
dc.contributor.authorLomax, Jo E.
dc.contributor.authorBianchetti, Christopher M.
dc.contributor.authorChang, Aram
dc.contributor.authorPhillips, George N.Jr.
dc.contributor.authorFox, Brian G.
dc.contributor.authorRaines, Ronald T.
dc.date.accessioned2015-03-16T16:56:10Z
dc.date.available2015-03-16T16:56:10Z
dc.date.issued2014
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.
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.
dc.identifier.doihttp://dx.doi.org/10.1016/j.jmb.2014.06.007
dc.identifier.urihttps://hdl.handle.net/1911/79354
dc.language.isoeng
dc.publisherElsevier
dc.rightsThis is an author's peer-reviewed final manuscript, as accepted by the publisher. The published article is copyrighted by Elsevier.
dc.subject.keywordleucine-rich repeat (LRR)
dc.subject.keywordprotein-protein interaction
dc.subject.keywordreactive oxygen species (ROS)
dc.subject.keywordredox homeostasis
dc.subject.keywordribonuclease
dc.titleFunctional Evolution of Ribonuclease Inhibitor: Insights from Birds and Reptiles
dc.typeJournal article
dc.type.dcmiText
dc.type.publicationpost-print
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