title: C-terminal unfolding of an amyloidogenic β2-microglobulin fragment: ΔN6β2-microglobulin.
abstract: OBJECTIVE
  A β2-microglobulin (β2m) fragment that lacks the first six amino acids, i.e., ΔN6β2-microglobulin (ΔN6β2m), is an endogenous, proteolytically derived, amyloidogenic fragment of β2m, the precursor protein in Aβ2M amyloidosis (dialysis-related amyloidosis). As reports suggest the importance of C-terminal unfolding for the amyloidogenicity of β2m, in this study we aimed to investigate conformational characteristics of ΔN6β2m related to amyloidogenicity. We also measured the concentration of an amyloidogenic intermediate of β2m with C-terminal unfolding (β2m92-99) in serum samples from 10 patients undergoing hemodialysis (HD).
  
  
  METHODS
  We utilized capillary electrophoretic analysis, surface plasmon resonance and enzyme-linked immunosorbent assay.
  
  
  CONCLUSIONS
  We confirmed the normal core structure of ΔN6β2m with a commercial monoclonal anti-β2m antibody. In addition, using the specific monoclonal antibody for the C-terminal peptide, i.e. mAb 92-99, we confirmed unfolding in the C-terminal region of ΔN6β2m. On the basis of these findings, we established an ELISA to measure β2m92-99 using ΔN6β2m as a standard molecule in circulation. However, we did not detect β2m92-99 in serum from 10 HD patients, despite the absence of uremic inhibitors in the serum.
authors.affiliation: Suiyukai Clinic , Kashihara, Nara , Japan .
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Motomiya
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Higashimoto
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Uji
authors.forename: Genki
authors.initials: G
authors.lastname: Suenaga
authors.forename: Yukio
authors.initials: Y
authors.lastname: Ando
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000737:chemistry; D006801:Humans; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood / Q000737:chemistry*; D011485:Protein Binding; D058767:Protein Unfolding; D006435:Renal Dialysis; D001613:beta 2-Microglobulin / Q000097:blood / Q000737:chemistry*
chemical_list: D000911:Antibodies, Monoclonal; D010446:Peptide Fragments; D001613:beta 2-Microglobulin
keywords: Amyloidogenicity; capillary electrophoresis; dialysis-related amyloidosis; enzyme-linked immunosorbent assay; hemodialysis; monoclonal antibody 92-99; surface plasmon resonance