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• W2532018695 endingPage "e0164740" @default.
• W2532018695 startingPage "e0164740" @default.
• W2532018695 abstract "The S100 proteins are a large family of signaling proteins that play critical roles in biology and disease. Many S100 proteins bind Zn2+, Cu2+, and/or Mn2+ as part of their biological functions; however, the evolutionary origins of binding remain obscure. One key question is whether divalent transition metal binding is ancestral, or instead arose independently on multiple lineages. To tackle this question, we combined phylogenetics with biophysical characterization of modern S100 proteins. We demonstrate an earlier origin for established S100 subfamilies than previously believed, and reveal that transition metal binding is widely distributed across the tree. Using isothermal titration calorimetry, we found that Cu2+ and Zn2+ binding are common features of the family: the full breadth of human S100 paralogs-as well as two early-branching S100 proteins found in the tunicate Oikopleura dioica-bind these metals with μM affinity and stoichiometries ranging from 1:1 to 3:1 (metal:protein). While binding is consistent across the tree, structural responses to binding are quite variable. Further, mutational analysis and structural modeling revealed that transition metal binding occurs at different sites in different S100 proteins. This is consistent with multiple origins of transition metal binding over the evolution of this protein family. Our work reveals an evolutionary pattern in which the overall phenotype of binding is a constant feature of S100 proteins, even while the site and mechanism of binding is evolutionarily labile." @default.
• W2532018695 created "2016-10-28" @default.
• W2532018695 creator A5029038777 @default.
• W2532018695 creator A5038227772 @default.
• W2532018695 creator A5047382666 @default.
• W2532018695 creator A5048475119 @default.
• W2532018695 date "2016-10-20" @default.
• W2532018695 modified "2023-09-27" @default.
• W2532018695 title "Multiple Evolutionary Origins of Ubiquitous Cu2+ and Zn2+ Binding in the S100 Protein Family" @default.
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