Arranged sevenfold: structural insights into the C-terminal oligomerization domain of human C4b-binding protein.

5.00
Hdl Handle:
http://hdl.handle.net/10033/301808
Title:
Arranged sevenfold: structural insights into the C-terminal oligomerization domain of human C4b-binding protein.
Authors:
Hofmeyer, Thomas; Schmelz, Stefan; Degiacomi, Matteo T; Dal Peraro, Matteo; Daneschdar, Matin; Scrima, Andrea; van den Heuvel, Joop; Heinz, Dirk W; Kolmar, Harald
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.
Affiliation:
Institute for Organic Chemistry and Biochemistry, Technische Universität Darmstadt, Petersenstraße 22, 64287 Darmstadt, Germany.
Citation:
Arranged sevenfold: structural insights into the C-terminal oligomerization domain of human C4b-binding protein. 2013, 425 (8):1302-17 J. Mol. Biol.
Journal:
Journal of molecular biology
Issue Date:
26-Apr-2013
URI:
http://hdl.handle.net/10033/301808
DOI:
10.1016/j.jmb.2012.12.017
PubMed ID:
23274142
Type:
Article
Language:
en
ISSN:
1089-8638
Appears in Collections:
research group of structural biology of autophagy (SBAU)

Full metadata record

DC FieldValue Language
dc.contributor.authorHofmeyer, Thomasen_GB
dc.contributor.authorSchmelz, Stefanen_GB
dc.contributor.authorDegiacomi, Matteo Ten_GB
dc.contributor.authorDal Peraro, Matteoen_GB
dc.contributor.authorDaneschdar, Matinen_GB
dc.contributor.authorScrima, Andreaen_GB
dc.contributor.authorvan den Heuvel, Joopen_GB
dc.contributor.authorHeinz, Dirk Wen_GB
dc.contributor.authorKolmar, Haralden_GB
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.en_GB
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

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