8BE5

Crystal structure of SOS1-KRasG12V-Nanobody22-Nanobody75

これはPDB形式変換不可エントリーです。

8BE5 の概要

• エントリーDOI: 10.2210/pdb8be5/pdb
• 分子名称: Son of sevenless homolog 1, Nanobody75, Isoform 2B of GTPase KRas, ... (5 entities in total)
• 機能のキーワード: complex, stabilizer, signaling protein
• 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: 109574.81

構造登録者

Fischer, B.,Wohlkonig, A.,Steyaert, J. (登録日: 2022-10-21, 公開日: 2023-11-01, 最終更新日: 2024-11-06)

主引用文献

Fischer, B.,Uchanski, T.,Sheryazdanova, A.,Gonzalez, S.,Volkov, A.N.,Brosens, E.,Zogg, T.,Kalichuk, V.,Ballet, S.,Versees, W.,Sablina, A.A.,Pardon, E.,Wohlkonig, A.,Steyaert, J.
Allosteric nanobodies to study the interactions between SOS1 and RAS.
Nat Commun, 15:6214-6214, 2024

PubMed Abstract: Protein-protein interactions (PPIs) are central in cell metabolism but research tools for the structural and functional characterization of these PPIs are often missing. Here we introduce broadly applicable immunization (Cross-link PPIs and immunize llamas, ChILL) and selection strategies (Display and co-selection, DisCO) for the discovery of diverse nanobodies that either stabilize or disrupt PPIs in a single experiment. We apply ChILL and DisCO to identify competitive, connective, or fully allosteric nanobodies that inhibit or facilitate the formation of the SOS1•RAS complex and modulate the nucleotide exchange rate on this pivotal GTPase in vitro as well as RAS signalling in cellulo. One of these connective nanobodies fills a cavity that was previously identified as the binding pocket for a series of therapeutic lead compounds. The long complementarity-determining region (CDR3) that penetrates this binding pocket serves as pharmacophore for extending the repertoire of potential leads.

PubMed: 39043660
DOI: 10.1038/s41467-024-50349-2

実験手法

X-RAY DIFFRACTION (3.13 Å)