f5102f216354bca6687483f59a11340a IntJouMolSci_a2022v23n24p15824.pdf f3b37775cad9de706c504d85be6b636ff15f3af8 IntJouMolSci_a2022v23n24p15824.pdf 6d36276be4741f693e0e8a2a2d996b83dc352c88b90ccab819a3f2a95a4f55b5 IntJouMolSci_a2022v23n24p15824.pdf Title: The Modular Architecture of Metallothioneins Facilitates Domain Rearrangements and Contributes to Their Evolvability in Metal-Accumulating Mollusks Subject: Protein domains are independent structural and functional modules that can rearrange to create new proteins. While the evolution of multidomain proteins through the shuffling of different preexisting domains has been well documented, the evolution of domain repeat proteins and the origin of new domains are less understood. Metallothioneins (MTs) provide a good case study considering that they consist of metal-binding domain repeats, some of them with a likely de novo origin. In mollusks, for instance, most MTs are bidomain proteins that arose by lineage-specific rearrangements between six putative domains: , 1, 2, 3, and . Some domains have been characterized in bivalves and gastropods, but nothing is known about the MTs and their domains of other Mollusca classes. To fill this gap, we investigated the metal-binding features of NpoMT1 of Nautilus pompilius (Cephalopoda class) and FcaMT1 of Falcidens caudatus (Caudofoveata class). Interestingly, whereas NpoMT1 consists of and 1 domains and has a prototypical Cd2+ preference, FcaMT1 has a singular preference for Zn2+ ions and a distinct domain composition, including a new Caudofoveata-specific domain. Overall, our results suggest that the modular architecture of MTs has contributed to MT evolution during mollusk diversification, and exemplify how modularity increases MT evolvability. Keywords: protein modularity; domain repeat proteins; de novo domains; sORFs and lncRNAs; Cephalopoda and Caudofoveata MTs Author: Sara Calatayud, Mario Garcia-Risco, Veronika Pedrini-Martha, Michael Niederwanger, Reinhard Dallinger, Òscar Palacios, Mercè Capdevila and Ricard Albalat Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Tue Dec 20 10:20:53 2022 CET ModDate: Tue Dec 20 10:42:18 2022 CET Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 12 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 1521191 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- JJTTKA+VnURWPalladioL Type 1 Custom yes yes no 10 0 KNPFEX+EURM10 Type 1 Builtin yes yes no 15 0 NSHEWV+URWPalladioL-Bold Type 1 Custom yes yes no 19 0 UEFAQT+URWPalladioL-Roma Type 1 Custom yes yes no 24 0 VUPSRZ+URWPalladioL-Ital Type 1 Custom 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PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 447 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4d3167f4 Item: Title: Results Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@ed9d034 Children: Item: Title: Characterization of Cephalopoda and Caudofoveata MTs: NpoMT1 and FcaMT1 Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@6121c9d6 Item: Title: Characterization of the and Domains of Cephalopoda and Caudofoveata MTs Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@87f383f Item: Title: Discussion Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4eb7f003 Children: Item: Title: Cephalopoda NpoMT1 and Caudofoveata FcaMT1, and the and Domains Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@eafc191 Item: Title: Biological Implications of the Cephalopoda and Caudofoveata MTs Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@612fc6eb Item: Title: Origin and Evolution of MT Domains Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1060b431 Item: Title: MT Modularity and Evolvability Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@612679d6 Item: Title: Materials and Methods Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@11758f2a Children: Item: Title: Production and Purification of Recombinant Metal-MT Complexes Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@e720b71 Item: Title: Analysis of Metal-MT Complexes Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1b26f7b2 Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@491cc5c9 Info: Title: The Modular Architecture of Metallothioneins Facilitates Domain Rearrangements and Contributes to Their Evolvability in Metal-Accumulating Mollusks Author: Sara Calatayud, Mario Garcia-Risco, Veronika Pedrini-Martha, Michael Niederwanger, Reinhard Dallinger, Òscar Palacios, Mercè Capdevila and Ricard Albalat Subject: Protein domains are independent structural and functional modules that can rearrange to create new proteins. While the evolution of multidomain proteins through the shuffling of different preexisting domains has been well documented, the evolution of domain repeat proteins and the origin of new domains are less understood. Metallothioneins (MTs) provide a good case study considering that they consist of metal-binding domain repeats, some of them with a likely de novo origin. In mollusks, for instance, most MTs are bidomain proteins that arose by lineage-specific rearrangements between six putative domains: , 1, 2, 3, and . Some domains have been characterized in bivalves and gastropods, but nothing is known about the MTs and their domains of other Mollusca classes. To fill this gap, we investigated the metal-binding features of NpoMT1 of Nautilus pompilius (Cephalopoda class) and FcaMT1 of Falcidens caudatus (Caudofoveata class). Interestingly, whereas NpoMT1 consists of and 1 domains and has a prototypical Cd2+ preference, FcaMT1 has a singular preference for Zn2+ ions and a distinct domain composition, including a new Caudofoveata-specific domain. Overall, our results suggest that the modular architecture of MTs has contributed to MT evolution during mollusk diversification, and exemplify how modularity increases MT evolvability. 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