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2W9D

Structure of Fab fragment of the ICSM 18 - anti-Prp therapeutic antibody at 1.57 A resolution.

2W9D の概要
エントリーDOI10.2210/pdb2w9d/pdb
関連するPDBエントリー2W9E
分子名称ICSM 18-ANTI-PRP THERAPEUTIC FAB HEAVY CHAIN, ICSM 18-ANTI-PRP THERAPEUTIC FAB LIGHT CHAIN, CALCIUM ION, ... (4 entities in total)
機能のキーワードimmune system, prion, prp, fab
由来する生物種MUS MUSCULUS
詳細
タンパク質・核酸の鎖数2
化学式量合計46573.72
構造登録者
主引用文献Antonyuk, S.V.,Trevitt, C.R.,Strange, R.W.,Jackson, G.S.,Sangar, D.,Batchelor, M.,Cooper, S.,Fraser, C.,Jones, S.,Georgiou, T.,Khalili-Shirazi, A.,Clarke, A.R.,Hasnain, S.S.,Collinge, J.
Crystal Structure of Human Prion Protein Bound to a Therapeutic Antibody.
Proc.Natl.Acad.Sci.USA, 106:2554-, 2009
Cited by
PubMed Abstract: Prion infection is characterized by the conversion of host cellular prion protein (PrP(C)) into disease-related conformers (PrP(Sc)) and can be arrested in vivo by passive immunization with anti-PrP monoclonal antibodies. Here, we show that the ability of an antibody to cure prion-infected cells correlates with its binding affinity for PrP(C) rather than PrP(Sc). We have visualized this interaction at the molecular level by determining the crystal structure of human PrP bound to the Fab fragment of monoclonal antibody ICSM 18, which has the highest affinity for PrP(C) and the highest therapeutic potency in vitro and in vivo. In this crystal structure, human PrP is observed in its native PrP(C) conformation. Interactions between neighboring PrP molecules in the crystal structure are mediated by close homotypic contacts between residues at position 129 that lead to the formation of a 4-strand intermolecular beta-sheet. The importance of this residue in mediating protein-protein contact could explain the genetic susceptibility and prion strain selection determined by polymorphic residue 129 in human prion disease, one of the strongest common susceptibility polymorphisms known in any human disease.
PubMed: 19204296
DOI: 10.1073/PNAS.0809170106
主引用文献が同じPDBエントリー
実験手法
X-RAY DIFFRACTION (1.57 Å)
構造検証レポート
Validation report summary of 2w9d
検証レポート(詳細版)ダウンロードをダウンロード

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件を2026-01-28に公開中

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