3DHM

Beta 2 microglobulin mutant D59P

Summary for 3DHM

• Entry DOI: 10.2210/pdb3dhm/pdb
• Related: 2z9t 3DHJ
• Descriptor: Beta-2-microglobulin (2 entities in total)
• Functional Keywords: beta-2-microglobulin, proline, amyloidosis, dra, beta fibrils, disease mutation, glycation, glycoprotein, immune response, immunoglobulin domain, mhc i, pyrrolidone carboxylic acid, secreted, immune system
• Biological source: Homo sapiens (Human)
• Cellular location: Secreted: P61769
• Total number of polymer chains: 1
• Total formula weight: 11861.38

Authors

Ricagno, S.,Colombo, M.,de Rosa, M.,Bolognesi, M.,Giorgetti, S.,Bellotti, V. (deposition date: 2008-06-18, release date: 2008-11-18, Last modification date: 2024-10-30)

Primary citation

Ricagno, S.,Colombo, M.,de Rosa, M.,Sangiovanni, E.,Giorgetti, S.,Raimondi, S.,Bellotti, V.,Bolognesi, M.
DE loop mutations affect beta2-microglobulin stability and amyloid aggregation
Biochem.Biophys.Res.Commun., 377:146-150, 2008

PubMed 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.

PubMed: 18835253
DOI: 10.1016/j.bbrc.2008.09.108

Experimental method

X-RAY DIFFRACTION (1.8 Å)