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DOI | 10.2210/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 | Antonyuk, S.V.,Trevitt, C.R.,Strange, R.W.,Jackson, G.S.,Sangar, D.,Batchelor, M.,Jones, S.,Georgiou, T.,Cooper, S.,Fraser, C.,Khalili-Shirazi, A.,Clarke, A.R.,Hasnain, S.S.,Collinge, J. (登録日: 2009-01-23, 公開日: 2009-02-03, 最終更新日: 2024-10-16) |
| 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: 19204296DOI: 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) |
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