4J8R

Structure of an octapeptide repeat of the prion protein bound to the POM2 Fab antibody fragment

4J8R の概要

• エントリーDOI: 10.2210/pdb4j8r/pdb
• 分子名称: Light chain of POM2 Fab, Heavy chain of POM2 Fab, Major prion protein, ... (4 entities in total)
• 機能のキーワード: immunoglobulin fold, fab, antibody, octapeptide repeat, mouse prion protein, immune system
• 由来する生物種: Mus musculus; 詳細
• 細胞内の位置: Cell membrane ; Lipid-anchor, GPI-anchor : P04925
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 95912.38

構造登録者

Swayampakula, M.,Baral, P.K.,Kav, N.N.V.,Aguzzi, A.,James, M.N.G. (登録日: 2013-02-14, 公開日: 2013-05-22, 最終更新日: 2024-11-06)

主引用文献

Swayampakula, M.,Baral, P.K.,Aguzzi, A.,Kav, N.N.,James, M.N.
The crystal structure of an octapeptide repeat of the Prion protein in complex with a Fab fragment of the POM2 antibody.
Protein Sci., 22:893-903, 2013

PubMed Abstract: Prion diseases are progressive, infectious neurodegenerative disorders caused primarily by the misfolding of the cellular prion protein (PrP(c)) into an insoluble, protease-resistant, aggregated isoform termed PrP(sc). In native conditions, PrP(c) has a structured C-terminal domain and a highly flexible N-terminal domain. A part of this N-terminal domain consists of 4-5 repeats of an unusual glycine-rich, eight amino acids long peptide known as the octapeptide repeat (OR) domain. In this article, we successfully report the first crystal structure of an OR of PrP(c) bound to the Fab fragment of the POM2 antibody. The structure was solved at a resolution of 2.3 Å by molecular replacement. Although several studies have previously predicted a β-turn-like structure of the unbound ORs, our structure shows an extended conformation of the OR when bound to a molecule of the POM2 Fab indicating that the bound Fab disrupts any putative native β turn conformation of the ORs. Encouraging results from several recent studies have shown that administering small molecule ligands or antibodies targeting the OR domain of PrP result in arresting the progress of peripheral prion infections both in ex vivo and in in vivo models. This makes the structural study of the interactions of POM2 Fab with the OR domain very important as it would help us to design smaller and tighter binding OR ligands.

PubMed: 23629842
DOI: 10.1002/pro.2270

実験手法

X-RAY DIFFRACTION (2.303 Å)