title: Controlled self-assembly of re-engineered insulin by Fe(II).
abstract: Self-assembly of proteins mediated by metal ions is crucial in biological systems and a better understanding and novel strategies for its control are important. An abiotic metal ion ligand in a protein offers the prospect of control of the oligomeric state, if a selectivity over binding to the native side chains can be achieved. Insulin binds Zn(II) to form a hexamer, which is important for its storage in vivo and in drug formulations. We have re-engineered an insulin variant to control its self-assembly by covalent attachment of 2,2'-bipyridine. The use of Fe(II) provided chemoselective binding over the native site, forming a homotrimer in a reversible manner, which was easily followed by the characteristic color of the Fe(II) complex. This provided the first well-defined insulin trimer and the first insulin variant for which self-assembly can be followed visually.
authors.affiliation: IGM, Faculty of Life Sciences, University of Copenhagen, Thorvaldsensvej 40, 1871 Frederiksberg, Denmark.
authors.forename: Henrik K
authors.initials: HK
authors.lastname: Munch
authors.forename: Søren Thiis
authors.initials: ST
authors.lastname: Heide
authors.forename: Niels Johan
authors.initials: NJ
authors.lastname: Christensen
authors.forename: Thomas
authors.initials: T
authors.lastname: Hoeg-Jensen
authors.forename: Peter W
authors.initials: PW
authors.lastname: Thulstrup
authors.forename: Knud J
authors.initials: KJ
authors.lastname: Jensen
mesh_terms: D015082:2,2'-Dipyridyl / Q000737:chemistry*; D005296:Ferrous Compounds / Q000737:chemistry*; D007328:Insulin / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D020836:Protein Structure, Quaternary; D015032:Zinc / Q000737:chemistry
chemical_list: D005296:Ferrous Compounds; D007328:Insulin; D015082:2,2'-Dipyridyl; D015032:Zinc