| DOI | Trouver le DOI : https://doi.org/10.1371/journal.pone.0030149 |
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| Auteur | Rechercher : Baral, T.N.1; Rechercher : Chao, S.-Y.; Rechercher : Li, S.1; Rechercher : Tanha, J.1; Rechercher : Arbabi-Ghahroudi, M.1; Rechercher : Zhang, J.1; Rechercher : Wang, S. |
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| Affiliation | - Conseil national de recherches du Canada. Institut des sciences biologiques du CNRC
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| Format | Texte, Article |
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| Sujet | 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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| Résumé | 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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| Date de publication | 2012 |
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| Dans | |
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| Langue | anglais |
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| Publications évaluées par des pairs | Oui |
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| Numéro NPARC | 21269192 |
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| Exporter la notice | Exporter en format RIS |
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| Signaler une correction | Signaler une correction (s'ouvre dans un nouvel onglet) |
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| Identificateur de l’enregistrement | 613c082e-b2e3-42a1-b53e-1c73aebc5aa7 |
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| Enregistrement créé | 2013-12-12 |
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| Enregistrement modifié | 2021-09-17 |
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