A camelid antibody fragment inhibits the formation of amyloid fibrils by human lysozyme

Mireille Dumoulin, Alexander M. Last, Aline Desmyter, Klaas Decanniere, Denis Canet, Göran Larsson, Andrew Spencer, David B. Archer, Jurgen Sasse, Serge Muyldermans, Lode Wyns, Christina Redfield, André Matagne, Carol V. Robinson and Christopher M. Dobson ()
Additional contact information
Mireille Dumoulin: University of Cambridge
Alexander M. Last: University of Oxford
Aline Desmyter: Vrije Universiteit Brussel
Klaas Decanniere: Vrije Universiteit Brussel
Denis Canet: University of Oxford
Göran Larsson: University of Cambridge
Andrew Spencer: Norwich Research Park, Colney
David B. Archer: University of Nottingham, University Park
Jurgen Sasse: Central Veterinary Research Laboratory
Serge Muyldermans: Vrije Universiteit Brussel
Lode Wyns: Vrije Universiteit Brussel
Christina Redfield: University of Oxford
André Matagne: Université de Liège
Carol V. Robinson: University of Cambridge
Christopher M. Dobson: University of Cambridge

Nature, 2003, vol. 424, issue 6950, 783-788

Abstract: 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 tissues1,2,3, often with serious pathological consequences. Non-neuropathic systemic amyloidosis4,5,6 is associated with single point mutations in the gene coding for human lysozyme. Here we report that a single-domain fragment of a camelid antibody7,8,9 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.

Date: 2003
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/nature01870 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:424:y:2003:i:6950:d:10.1038_nature01870

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/nature01870

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().