Format

Send to:

Choose Destination
See comment in PubMed Commons below
Biochem Biophys Res Commun. 2008 Dec 5;377(1):146-50. doi: 10.1016/j.bbrc.2008.09.108. Epub 2008 Oct 1.

DE loop mutations affect beta2-microglobulin stability and amyloid aggregation.

Author information

  • 1Department of Biomolecular Sciences and Biotechnology, CNR-INFM and CIMAINA, University of Milano, Milano, Italy.

Abstract

Beta2-microglobulin (beta2m) is the light chain component of class I major histocompatibility complex (MHC-I). beta2m is an intrinsically amyloidogenic protein that can assemble into amyloid fibrils in vitro and in vivo. Several recent reports suggested that the polypeptide loop comprised between beta-strands D and E of beta2m is important for protein stability and for the protein propensity to aggregate as amyloid fibrils. In particular, the roles of Trp60 for MHC-I assembly and beta2m stability have been highlighted by showing that the beta2m Trp60-->Gly mutant is more stable and less prone to aggregation than the wild type protein. To further analyse such properties, the Trp60-->Cys and Asp59-->Pro beta2m mutants have been expressed, purified, and their crystal structures determined. The stability to thermal denaturation and propensity to fibrillar aggregation have also been analysed. The experimental evidences gathered on the two mutants reinforce the hypothesis that conformational strain in the DE loop can affect beta2m stability and amyloid aggregation properties.

PMID:
18835253
[PubMed - indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Write to the Help Desk