4PGJ

Human heavy-chain domain antibody in complex with hen egg-white lysozyme

4PGJ の概要

• エントリーDOI: 10.2210/pdb4pgj/pdb
• 分子名称: Human heavy chain domain antibody, Lysozyme C (2 entities in total)
• 機能のキーワード: antibody human dab cleft binder dab-hel complex, immune system-hydrolase complex, immune system/hydrolase
• 由来する生物種: Homo sapiens; 詳細
• 細胞内の位置: Secreted: P00698
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 55009.36

構造登録者

Christ, D.,Langley, D.B.,Rouet, R. (登録日: 2014-05-02, 公開日: 2015-03-11, 最終更新日: 2024-10-23)

主引用文献

Rouet, R.,Dudgeon, K.,Christie, M.,Langley, D.,Christ, D.
Fully Human VH Single Domains That Rival the Stability and Cleft Recognition of Camelid Antibodies.
J.Biol.Chem., 290:11905-11917, 2015

PubMed Abstract: Human VH single domains represent a promising class of antibody fragments with applications as therapeutic modalities. Unfortunately, isolated human VH domains also generally display poor biophysical properties and a propensity to aggregate. This has encouraged the development of non-human antibody domains as alternative means of antigen recognition and, in particular, camelid (VHH) domains. Naturally devoid of light chain partners, these domains are characterized by favorable biophysical properties and propensity for cleft binding, a highly desirable characteristic, allowing the targeting of cryptic epitopes. In contrast, previously reported structures of human VH single domains had failed to recapitulate this property. Here we report the engineering and characterization of phage display libraries of stable human VH domains and the selection of binders against a diverse set of antigens. Unlike "camelized" human domains, the domains do not rely on potentially immunogenic framework mutations and maintain the structure of the VH/VL interface. Structure determination in complex with hen egg white lysozyme revealed an extended VH binding interface, with complementarity-determining region 3 deeply penetrating into the active site cleft, highly reminiscent of what has been observed for camelid domains. Taken together, our results demonstrate that fully human VH domains can be constructed that are not only stable and well expressed but also rival the cleft binding properties of camelid antibodies.

PubMed: 25737448
DOI: 10.1074/jbc.M114.614842

実験手法

X-RAY DIFFRACTION (2.6 Å)