| DOI | Resolve DOI: https://doi.org/10.1371/journal.pone.0030149 |
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| Author | Search for: Baral, T.N.1; Search for: Chao, S.-Y.; Search for: Li, S.1; Search for: Tanha, J.1; Search for: Arbabi-Ghahroudi, M.1; Search for: Zhang, J.1; Search for: Wang, S. |
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| Affiliation | - National Research Council of Canada. NRC Institute for Biological Sciences
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| Format | Text, Article |
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| Subject | epidermal 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; 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; 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; 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 |
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| Abstract | Single-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. |
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| Publication date | 2012 |
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| In | |
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| Language | English |
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| Peer reviewed | Yes |
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| NPARC number | 21269192 |
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| Export citation | Export as RIS |
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| Report a correction | Report a correction (opens in a new tab) |
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| Record identifier | 613c082e-b2e3-42a1-b53e-1c73aebc5aa7 |
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| Record created | 2013-12-12 |
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| Record modified | 2021-09-17 |
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