title: Wild type beta-2 microglobulin and DE loop mutants display a common fibrillar architecture.
abstract: Beta-2 microglobulin (β2m) is the protein responsible for a pathologic condition known as dialysis related amyloidosis. In recent years an important role has been assigned to the peptide loop linking strands D and E (DE loop) in determining β2m stability and amyloid propensity. Several mutants of the DE loop have been studied, showing a good correlation between DE loop geometrical strain, protein stability and aggregation propensity. However, it remains unclear whether the aggregates formed by wild type (wt) β2m and by the DE loop variants are of the same kind, or whether the mutations open new aggregation pathways. In order to address this question, fibrillar samples of wt and mutated β2m variants have been analysed by means of atomic force microscopy and infrared spectroscopy. The data here reported indicate that the DE loop mutants form aggregates with morphology and structural organisation very similar to the wt protein. Therefore, the main effect of β2m DE loop mutations is proposed to stem from the different stabilities of the native fold. Considerations on the structural role of the DE loop in the free monomeric β2m and as part of the Major Histocompatibility Complex are also presented.
authors: Dipartimento di Fisica G. Occhialini and Dipartimento di Biotecnologie e Bioscienze, Università di Milano-Bicocca, P.zza della Scienza 2, Milano, Italy.
authors: Antonino
authors: A
authors: Natalello
authors: Dipartimento di Fisica, Università di Genova, via Dodecaneso 33, Genova, Italy.
authors: Annalisa
authors: A
authors: Relini
authors: Dipartimento di Fisica, Università di Genova, via Dodecaneso 33, Genova, Italy.
authors: Amanda
authors: A
authors: Penco
authors: Dipartimento di Bioscienze, Università di Milano, Via Celoria 26, Milano, Italy.
authors: Levon
authors: L
authors: Halabelian
authors: Dipartimento di Bioscienze, Università di Milano, Via Celoria 26, Milano, Italy; CIMAINA e Istituto CNR di Biofisica, Milano, Italy.
authors: Martino
authors: M
authors: Bolognesi
authors: Dipartimento di Fisica G. Occhialini and Dipartimento di Biotecnologie e Bioscienze, Università di Milano-Bicocca, P.zza della Scienza 2, Milano, Italy.
authors: Silvia Maria
authors: SM
authors: Doglia
authors: Dipartimento di Bioscienze, Università di Milano, Via Celoria 26, Milano, Italy.
authors: Stefano
authors: S
authors: Ricagno
mesh_terms: D000682:Amyloid / Q000737:chemistry* / Q000378:metabolism; D000686:Amyloidosis / Q000209:etiology / Q000378:metabolism*; D006801:Humans; D018625:Microscopy, Atomic Force; D008958:Models, Molecular; D009154:Mutation / Q000235:genetics; D066263:Protein Aggregation, Pathological / Q000235:genetics*; D055550:Protein Stability; D006435:Renal Dialysis / Q000009:adverse effects*; D013055:Spectrophotometry, Infrared; D001613:beta 2-Microglobulin / Q000737:chemistry* / Q000378:metabolism
chemical_list: D000682:Amyloid; D001613:beta 2-Microglobulin