1OP9

Complex of human lysozyme with camelid VHH HL6 antibody fragment

1OP9 の概要

• エントリーDOI: 10.2210/pdb1op9/pdb
• 分子名称: HL6 camel VHH fragment, Lysozyme C (3 entities in total)
• 機能のキーワード: antigen-antibody complex, immunoglobulin, amyloid fibril formation inhibition, hydrolase
• 由来する生物種: Camelus dromedarius (Arabian camel); 詳細
• 細胞内の位置: Secreted: P61626
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 27759.94

構造登録者

Dumoulin, M.,Last, A.M.,Desmyter, A.,Decanniere, K.,Canet, D.,Larsson, G.,Spencer, A.,Archer, D.B.,Sasse, J.,Muyldermans, S.,Wyns, L.,Redfield, C.,Matagne, A.,Robinson, C.V.,Dobson, C.M. (登録日: 2003-03-05, 公開日: 2003-10-14, 最終更新日: 2024-11-06)

主引用文献

Dumoulin, M.,Last, A.M.,Desmyter, A.,Decanniere, K.,Canet, D.,Larsson, G.,Spencer, A.,Archer, D.B.,Sasse, J.,Muyldermans, S.,Wyns, L.,Redfield, C.,Matagne, A.,Robinson, C.V.,Dobson, C.M.
A camelid antibody fragment inhibits the formation of amyloid fibrils by human lysozyme
Nature, 424:783-788, 2003

PubMed Abstract: Amyloid diseases are characterized by an aberrant assembly of a specific protein or protein fragment into fibrils and plaques that are deposited in various organs and tissues, often with serious pathological consequences. Non-neuropathic systemic amyloidosis is associated with single point mutations in the gene coding for human lysozyme. Here we report that a single-domain fragment of a camelid antibody raised against wild-type human lysozyme inhibits the in vitro aggregation of its amyloidogenic variant, D67H. Our structural studies reveal that the epitope includes neither the site of mutation nor most residues in the region of the protein structure that is destabilized by the mutation. Instead, the binding of the antibody fragment achieves its effect by restoring the structural cooperativity characteristic of the wild-type protein. This appears to occur at least in part through the transmission of long-range conformational effects to the interface between the two structural domains of the protein. Thus, reducing the ability of an amyloidogenic protein to form partly unfolded species can be an effective method of preventing its aggregation, suggesting approaches to the rational design of therapeutic agents directed against protein deposition diseases.

PubMed: 12917687
DOI: 10.1038/nature01870

実験手法

X-RAY DIFFRACTION (1.86 Å)