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

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.

SUBMITTER: Baral TN

PROVIDER: S-EPMC3257273 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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

Baral Toya Nath TN Chao Shi-Yu SY Li Shenghua S Tanha Jamshid J Arbabi-Ghahroudi Mehdi M Zhang Jianbing J Wang Shuying S

PloS one 20120112 1

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 ...[more]

PMID: 22253912

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