4KRN

Nanobody/VHH domain EgA1

4KRN の概要

• エントリーDOI: 10.2210/pdb4krn/pdb
• 関連するPDBエントリー: 4KRL 4KRM 4KRO 4KRP
• 分子名称: Nanobody/VHH domain EgA1, SULFATE ION (3 entities in total)
• 機能のキーワード: nanobody, vhh domain, camelid vh domain, antibody, immune system
• 由来する生物種: Lama glama (llama)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 15642.24

構造登録者

Ferguson, K.M.,Schmitz, K.R. (登録日: 2013-05-16, 公開日: 2013-08-28, 最終更新日: 2024-11-06)

主引用文献

Schmitz, K.R.,Bagchi, A.,Roovers, R.C.,van Bergen En Henegouwen, P.M.,Ferguson, K.M.
Structural Evaluation of EGFR Inhibition Mechanisms for Nanobodies/VHH Domains.
Structure, 21:1214-1224, 2013

PubMed Abstract: The epidermal growth factor receptor (EGFR) is implicated in human cancers and is the target of several classes of therapeutic agents, including antibody-based drugs. Here, we describe X-ray crystal structures of the extracellular region of EGFR in complex with three inhibitory nanobodies, the variable domains of heavy chain only antibodies (VHH). VHH domains, the smallest natural antigen-binding modules, are readily engineered for diagnostic and therapeutic applications. All three VHH domains prevent ligand-induced EGFR activation, but use two distinct mechanisms. 7D12 sterically blocks ligand binding to EGFR in a manner similar to that of cetuximab. EgA1 and 9G8 bind an epitope near the EGFR domain II/III junction, preventing receptor conformational changes required for high-affinity ligand binding and dimerization. This epitope is accessible to the convex VHH paratope but inaccessible to the flatter paratope of monoclonal antibodies. Appreciating the modes of binding and inhibition of these VHH domains will aid in developing them for tumor imaging and/or cancer therapy.

PubMed: 23791944
DOI: 10.1016/j.str.2013.05.008

実験手法

X-RAY DIFFRACTION (1.553 Å)