8UKV

Crystal structure of nanobody/VHH domain of 34E5 in complex with the extracellular region of the epidermal growth factor variant III (EGFRvIII)

8UKV の概要

• エントリーDOI: 10.2210/pdb8ukv/pdb
• 関連するPDBエントリー: 8UKW 8UKX
• 分子名称: Epidermal growth factor receptor, Nanobody/VHH domain 34E5, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total)
• 機能のキーワード: cell surface receptor, glycoprotein, extracellular, glioblastoma, oncogenic variant, nanobody, vhh domain, camelid vh domain, antibody, antigen, antibody complex, transferase-immune system complex, transferase, transferase/immune system
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 111436.20

構造登録者

Stayrook, S.E.,Ferguson, K.M.,Bagchi, A. (登録日: 2023-10-15, 公開日: 2024-06-19, 最終更新日: 2024-10-16)

主引用文献

Bagchi, A.,Stayrook, S.E.,Xenaki, K.T.,Starbird, C.A.,Doulkeridou, S.,El Khoulati, R.,Roovers, R.C.,Schmitz, K.R.,van Bergen En Henegouwen, P.M.P.,Ferguson, K.M.
Structural insights into the role and targeting of EGFRvIII.
Structure, 32:1367-, 2024

PubMed Abstract: The epidermal growth factor receptor (EGFR) is a well-known oncogenic driver in lung and other cancers. In glioblastoma multiforme (GBM), the EGFR deletion variant III (EGFRvIII) is frequently found alongside EGFR amplification. Agents targeting the EGFR axis have shown limited clinical benefits in GBM and the role of EGFRvIII in GBM is poorly understood. To shed light on the role of EGFRvIII and its potential as a therapeutic target, we determined X-ray crystal structures of a monomeric EGFRvIII extracellular region (ECR). The EGFRvIII ECR resembles the unliganded conformation of EGFR, including the orientation of the C-terminal region of domain II. Domain II is mostly disordered, but the ECR structure is compact. We selected a nanobody with preferential binding to EGFRvIII relative to EGFR and structurally defined an epitope on domain IV that is occluded in the unliganded intact EGFR. These findings suggest new avenues for EGFRvIII targeting in GBM.

PubMed: 38908376
DOI: 10.1016/j.str.2024.05.018

実験手法

X-RAY DIFFRACTION (2.94 Å)