Crystal structure of a human single domain antibody dimer formed through V H-V H non-covalent interactions

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DOIResolve DOI: http://doi.org/10.1371/journal.pone.0030149
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TypeArticle
Journal titlePLoS ONE
ISSN1932-6203
Volume7
Issue1
Article numbere30149
Subjectepidermal growth factor receptor 2 single domain antibody Gr3; epidermal growth factor receptor 2 single domain antibody Gr6; epidermal growth factor receptor antibody; homodimer; unclassified drug; antibody; epidermal growth factor receptor 2; HER2 protein, human; article; controlled study; covalent bond; crystal structure; dimerization; gel permeation chromatography; hydrophobicity; immunoglobulin variable region; molecular cloning; molecular interaction; molecular library; phage display; protein analysis; protein assembly; protein isolation; surface plasmon resonance; thermostability; amino acid sequence; antibody specificity; chemical phenomena; chemical structure; chemistry; human; immunology; metabolism; molecular genetics; protein binding; protein multimerization; protein secondary structure; protein tertiary structure; solution and solubility; transition temperature; X ray crystallography; Amino Acid Sequence; Antibodies; Antibody Specificity; Crystallography, X-Ray; Humans; Hydrophobic and Hydrophilic Interactions; Immunoglobulin Variable Region; Models, Molecular; Molecular Sequence Data; Protein Binding; Protein Multimerization; Protein Structure, Secondary; Protein Structure, Tertiary; Receptor, erbB-2; Solutions; Transition Temperature
AbstractSingle-domain antibodies (sdAbs) derived from human V H are considered to be less soluble and prone to aggregate which makes it difficult to determine the crystal structures. In this study, we isolated and characterized two anti-human epidermal growth factor receptor-2 (HER2) sdAbs, Gr3 and Gr6, from a synthetic human V H phage display library. Size exclusion chromatography and surface plasmon resonance analyses demonstrated that Gr3 is a monomer, but that Gr6 is a strict dimer. To understand this different molecular behavior, we solved the crystal structure of Gr6 to 1.6 Å resolution. The crystal structure revealed that the homodimer assembly of Gr6 closely mimics the V H-V L heterodimer of immunoglobulin variable domains and the dimerization interface is dominated by hydrophobic interactions. © 2012 Baral et al.
Publication date
LanguageEnglish
AffiliationNational Research Council Canada (NRC-CNRC); NRC Institute for Biological Sciences (IBS-ISB)
Peer reviewedYes
NPARC number21269192
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Record identifier613c082e-b2e3-42a1-b53e-1c73aebc5aa7
Record created2013-12-12
Record modified2016-05-09
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