title: Arranged sevenfold: structural insights into the C-terminal oligomerization domain of human C4b-binding protein.
abstract: The complement system as a major part of innate immunity is the first line of defense against invading microorganisms. Orchestrated by more than 60 proteins, its major task is to discriminate between host cells and pathogens and to initiate immune response. Additional recognition of necrotic or apoptotic cells demands a fine-tune regulation of this powerful system. C4b-binding protein (C4BP) is the major inhibitor of the classical complement and lectin pathway. The crystal structure of the human C4BP oligomerization domain in its 7α isoform and molecular simulations provide first structural insights of C4BP oligomerization. The heptameric core structure is stabilized by intermolecular disulfide bonds. In addition, thermal shift assays indicate that layers of electrostatic interactions mainly contribute to the extraordinary thermodynamic stability of the complex. These findings make C4BP a promising scaffold for multivalent ligand display with applications in immunology and biological chemistry.
authors.affiliation: Institute for Organic Chemistry and Biochemistry, Technische Universität Darmstadt, Petersenstraße 22, 64287 Darmstadt, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Hofmeyer
authors.forename: Stefan
authors.initials: S
authors.lastname: Schmelz
authors.forename: Matteo T
authors.initials: MT
authors.lastname: Degiacomi
authors.forename: Matteo
authors.initials: M
authors.lastname: Dal Peraro
authors.forename: Matin
authors.initials: M
authors.lastname: Daneschdar
authors.forename: Andrea
authors.initials: A
authors.lastname: Scrima
authors.forename: Joop
authors.initials: J
authors.lastname: van den Heuvel
authors.forename: Dirk W
authors.initials: DW
authors.lastname: Heinz
authors.forename: Harald
authors.initials: H
authors.lastname: Kolmar
mesh_terms: D050716:Complement C4b-Binding Protein / Q000737:chemistry*; D018360:Crystallography, X-Ray; D006801:Humans; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D011487:Protein Conformation; D055503:Protein Multimerization; D055672:Static Electricity; D013816:Thermodynamics
chemical_list: C055609:C4BPA protein, human; D050716:Complement C4b-Binding Protein