8G3K

Cryo-EM imaging scaffold subunits A and B used to display KRAS G12C complex with GDP

8G3K の概要

• エントリーDOI: 10.2210/pdb8g3k/pdb
• 関連するPDBエントリー: 8G42
• EMDBエントリー: 29700
• 分子名称: Cob_adeno_trans domain-containing protein, Cryo-EM imaging scaffold subunit B with DARPin - RCG-33 (2 entities in total)
• 機能のキーワード: cryoem imaging scaffold, cancer, gtpase, structural protein
• 由来する生物種: Thermoplasma acidophilum; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 55625.84

構造登録者

Castells-Graells, R.,Sawaya, M.R.,Yeates, T.O. (登録日: 2023-02-08, 公開日: 2023-08-09, 最終更新日: 2023-09-27)

主引用文献

Castells-Graells, R.,Meador, K.,Arbing, M.A.,Sawaya, M.R.,Gee, M.,Cascio, D.,Gleave, E.,Debreczeni, J.E.,Breed, J.,Leopold, K.,Patel, A.,Jahagirdar, D.,Lyons, B.,Subramaniam, S.,Phillips, C.,Yeates, T.O.
Cryo-EM structure determination of small therapeutic protein targets at 3 angstrom -resolution using a rigid imaging scaffold.
Proc.Natl.Acad.Sci.USA, 120:e2305494120-e2305494120, 2023

PubMed Abstract: Cryoelectron microscopy (Cryo-EM) has enabled structural determination of proteins larger than about 50 kDa, including many intractable by any other method, but it has largely failed for smaller proteins. Here, we obtain structures of small proteins by binding them to a rigid molecular scaffold based on a designed protein cage, revealing atomic details at resolutions reaching 2.9 Å. We apply this system to the key cancer signaling protein KRAS (19 kDa in size), obtaining four structures of oncogenic mutational variants by cryo-EM. Importantly, a structure for the key G12C mutant bound to an inhibitor drug (AMG510) reveals significant conformational differences compared to prior data in the crystalline state. The findings highlight the promise of cryo-EM scaffolds for advancing the design of drug molecules against small therapeutic protein targets in cancer and other human diseases.

PubMed: 37669364
DOI: 10.1073/pnas.2305494120

実験手法

ELECTRON MICROSCOPY (2.2 Å)