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

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, fr...

Full description

Bibliographic Details
Main Authors: Toya Nath Baral, Shi-Yu Chao, Shenghua Li, Jamshid Tanha, Mehdi Arbabi-Ghahroudi, Jianbing Zhang, Shuying Wang
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2012-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3257273?pdf=render
id doaj-37bdc78d6f0c4c1da1d54425b52176c8
record_format Article
spelling doaj-37bdc78d6f0c4c1da1d54425b52176c82020-11-25T02:47:26ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0171e3014910.1371/journal.pone.0030149Crystal structure of a human single domain antibody dimer formed through V(H)-V(H) non-covalent interactions.Toya Nath BaralShi-Yu ChaoShenghua LiJamshid TanhaMehdi Arbabi-GhahroudiJianbing ZhangShuying WangSingle-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.http://europepmc.org/articles/PMC3257273?pdf=render
collection DOAJ
language English
format Article
sources DOAJ
author Toya Nath Baral
Shi-Yu Chao
Shenghua Li
Jamshid Tanha
Mehdi Arbabi-Ghahroudi
Jianbing Zhang
Shuying Wang
spellingShingle Toya Nath Baral
Shi-Yu Chao
Shenghua Li
Jamshid Tanha
Mehdi Arbabi-Ghahroudi
Jianbing Zhang
Shuying Wang
Crystal structure of a human single domain antibody dimer formed through V(H)-V(H) non-covalent interactions.
PLoS ONE
author_facet Toya Nath Baral
Shi-Yu Chao
Shenghua Li
Jamshid Tanha
Mehdi Arbabi-Ghahroudi
Jianbing Zhang
Shuying Wang
author_sort Toya Nath Baral
title Crystal structure of a human single domain antibody dimer formed through V(H)-V(H) non-covalent interactions.
title_short Crystal structure of a human single domain antibody dimer formed through V(H)-V(H) non-covalent interactions.
title_full Crystal structure of a human single domain antibody dimer formed through V(H)-V(H) non-covalent interactions.
title_fullStr Crystal structure of a human single domain antibody dimer formed through V(H)-V(H) non-covalent interactions.
title_full_unstemmed Crystal structure of a human single domain antibody dimer formed through V(H)-V(H) non-covalent interactions.
title_sort crystal structure of a human single domain antibody dimer formed through v(h)-v(h) non-covalent interactions.
publisher Public Library of Science (PLoS)
series PLoS ONE
issn 1932-6203
publishDate 2012-01-01
description 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.
url http://europepmc.org/articles/PMC3257273?pdf=render
work_keys_str_mv AT toyanathbaral crystalstructureofahumansingledomainantibodydimerformedthroughvhvhnoncovalentinteractions
AT shiyuchao crystalstructureofahumansingledomainantibodydimerformedthroughvhvhnoncovalentinteractions
AT shenghuali crystalstructureofahumansingledomainantibodydimerformedthroughvhvhnoncovalentinteractions
AT jamshidtanha crystalstructureofahumansingledomainantibodydimerformedthroughvhvhnoncovalentinteractions
AT mehdiarbabighahroudi crystalstructureofahumansingledomainantibodydimerformedthroughvhvhnoncovalentinteractions
AT jianbingzhang crystalstructureofahumansingledomainantibodydimerformedthroughvhvhnoncovalentinteractions
AT shuyingwang crystalstructureofahumansingledomainantibodydimerformedthroughvhvhnoncovalentinteractions
_version_ 1724753588155056128