6SUZ

Human prion protein (PrP) fragment 119-231 (G127V V129 variant) complexed to ICSM 18 (anti-Prp therapeutic antibody) Fab fragment

6SUZ の概要

• エントリーDOI: 10.2210/pdb6suz/pdb
• 分子名称: Major prion protein, ICSM 18-ANTI-PRP THERAPEUTIC FAB HEAVY CHAIN, ICSM 18-ANTI-PRP THERAPEUTIC FAB LIGHT CHAIN, ... (5 entities in total)
• 機能のキーワード: prion, protein binding
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 58183.49

構造登録者

Conners, R. (登録日: 2019-09-17, 公開日: 2020-08-12, 最終更新日: 2024-11-20)

主引用文献

Hosszu, L.L.P.,Conners, R.,Sangar, D.,Batchelor, M.,Sawyer, E.B.,Fisher, S.,Cliff, M.J.,Hounslow, A.M.,McAuley, K.,Leo Brady, R.,Jackson, G.S.,Bieschke, J.,Waltho, J.P.,Collinge, J.
Structural effects of the highly protective V127 polymorphism on human prion protein.
Commun Biol, 3:402-402, 2020

PubMed Abstract: Prion diseases, a group of incurable, lethal neurodegenerative disorders of mammals including humans, are caused by prions, assemblies of misfolded host prion protein (PrP). A single point mutation (G127V) in human PrP prevents prion disease, however the structural basis for its protective effect remains unknown. Here we show that the mutation alters and constrains the PrP backbone conformation preceding the PrP β-sheet, stabilising PrP dimer interactions by increasing intermolecular hydrogen bonding. It also markedly changes the solution dynamics of the β2-α2 loop, a region of PrP structure implicated in prion transmission and cross-species susceptibility. Both of these structural changes may affect access to protein conformers susceptible to prion formation and explain its profound effect on prion disease.

PubMed: 32728168
DOI: 10.1038/s42003-020-01126-6

実験手法

X-RAY DIFFRACTION (2.5 Å)