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dc.contributor.authorHofmeyer, Thomas
dc.contributor.authorSchmelz, Stefan
dc.contributor.authorDegiacomi, Matteo T
dc.contributor.authorDal Peraro, Matteo
dc.contributor.authorDaneschdar, Matin
dc.contributor.authorScrima, Andrea
dc.contributor.authorvan den Heuvel, Joop
dc.contributor.authorHeinz, Dirk W
dc.contributor.authorKolmar, Harald
dc.date.accessioned2013-09-18T14:16:21Z
dc.date.available2013-09-18T14:16:21Z
dc.date.issued2013-04-26
dc.identifier.citationArranged sevenfold: structural insights into the C-terminal oligomerization domain of human C4b-binding protein. 2013, 425 (8):1302-17 J. Mol. Biol.en_GB
dc.identifier.issn1089-8638
dc.identifier.pmid23274142
dc.identifier.doi10.1016/j.jmb.2012.12.017
dc.identifier.urihttp://hdl.handle.net/10033/301808
dc.description.abstractThe 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.
dc.language.isoenen
dc.rightsArchived with thanks to Journal of molecular biologyen_GB
dc.subject.meshComplement C4b-Binding Proteinen_GB
dc.subject.meshCrystallography, X-Rayen_GB
dc.subject.meshHumansen_GB
dc.subject.meshModels, Molecularen_GB
dc.subject.meshMolecular Dynamics Simulationen_GB
dc.subject.meshProtein Conformationen_GB
dc.subject.meshProtein Multimerizationen_GB
dc.subject.meshStatic Electricityen_GB
dc.subject.meshThermodynamicsen_GB
dc.titleArranged sevenfold: structural insights into the C-terminal oligomerization domain of human C4b-binding protein.en
dc.typeArticleen
dc.contributor.departmentInstitute for Organic Chemistry and Biochemistry, Technische Universität Darmstadt, Petersenstraße 22, 64287 Darmstadt, Germany.en_GB
dc.identifier.journalJournal of molecular biologyen_GB
refterms.dateFOA2018-06-13T19:27:11Z
html.description.abstractThe 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.


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