Change search
ReferencesLink to record
Permanent link

Direct link
A camelid antibody fragment inhibits the formation of amyloid fibrils by human lysozyme.
Show others and affiliations
2003 (English)In: Nature, ISSN 1476-4687, Vol. 424, no 6950, 783-8 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2003. Vol. 424, no 6950, 783-8 p.
URN: urn:nbn:se:umu:diva-42938DOI: 10.1038/nature01870PubMedID: 12917687OAI: diva2:410783
Available from: 2011-04-14 Created: 2011-04-14 Last updated: 2011-04-14

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Larsson, Göran

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 32 hits
ReferencesLink to record
Permanent link

Direct link