title: Two independently folding units of Plasmodium profilin suggest evolution via gene fusion.
abstract: Gene fusion is a common mechanism of protein evolution that has mainly been discussed in the context of multidomain or symmetric proteins. Less is known about fusion of ancestral genes to produce small single-domain proteins. Here, we show with a domain-swapped mutant Plasmodium profilin that this small, globular, apparently single-domain protein consists of two foldons. The separation of binding sites for different protein ligands in the two halves suggests evolution via an ancient gene fusion event, analogous to the formation of multidomain proteins. Finally, the two fragments can be assembled together after expression as two separate gene products. The possibility to engineer both domain-swapped dimers and half-profilins that can be assembled back to a full profilin provides perspectives for engineering of novel protein folds, e.g., with different scaffolding functions.
authors.affiliation: Faculty of Biochemistry and Molecular Medicine, University of Oulu, P.O. Box 5400, 90014, Oulu, Finland.
authors.forename: Saligram Prabhakar
authors.initials: SP
authors.lastname: Bhargav
authors.affiliation: Faculty of Biochemistry and Molecular Medicine, University of Oulu, P.O. Box 5400, 90014, Oulu, Finland.
authors.forename: Juha
authors.initials: J
authors.lastname: Vahokoski
authors.affiliation: Helmholtz Centre for Infection Research, Notkestrasse 85, 22607, Hamburg, Germany.|German Electron Synchrotron (DESY), Notkestrasse 85, 22607, Hamburg, Germany.
authors.forename: Juha Pekka
authors.initials: JP
authors.lastname: Kallio
authors.affiliation: Centre for Bioinformatics, University of Hamburg, Bundesstrasse 43, 20146, Hamburg, Germany.
authors.forename: Andrew E
authors.initials: AE
authors.lastname: Torda
authors.affiliation: Faculty of Biochemistry and Molecular Medicine, University of Oulu, P.O. Box 5400, 90014, Oulu, Finland.|Biocenter Oulu, University of Oulu, P.O. Box 5000, 90014, Oulu, Finland.|Department of Biomedicine, University of Bergen, Jonas Lies vei 91, 5009, Bergen, Norway.
authors.forename: Petri
authors.initials: P
authors.lastname: Kursula
authors.affiliation: Faculty of Biochemistry and Molecular Medicine, University of Oulu, P.O. Box 5400, 90014, Oulu, Finland. inari.kursula@oulu.fi.|Helmholtz Centre for Infection Research, Notkestrasse 85, 22607, Hamburg, Germany. inari.kursula@oulu.fi.|German Electron Synchrotron (DESY), Notkestrasse 85, 22607, Hamburg, Germany. inari.kursula@oulu.fi.|Department of Biomedicine, University of Bergen, Jonas Lies vei 91, 5009, Bergen, Norway. inari.kursula@oulu.fi.
authors.forename: Inari
authors.initials: I
authors.lastname: Kursula
mesh_terms: D002942:Circular Dichroism; D018360:Crystallography, X-Ray; D019143:Evolution, Molecular; D005091:Exons; D050939:Gene Fusion; D007438:Introns; D008958:Models, Molecular; D009154:Mutation; D010963:Plasmodium falciparum / Q000737:chemistry*; D051304:Profilins / Q000737:chemistry* / Q000235:genetics*; D017510:Protein Folding; D055503:Protein Multimerization; D021122:Protein Subunits / Q000737:chemistry / Q000235:genetics; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics; D053838:Scattering, Small Angle; D014961:X-Ray Diffraction
chemical_list: D051304:Profilins; D021122:Protein Subunits; D015800:Protozoan Proteins
keywords: Actin-binding protein; Crystal structure; Modular; Protein interaction; Sequence analysis; Small-angle X-ray scattering; β-Hairpin