title: Beta2-microglobulin isoforms display an heterogeneous affinity for type I collagen.
abstract: It has been claimed that beta2-microglobulin (beta2-m) interacts with type I and type II collagen, and this property has been linked to the tissue specificity of the beta2-m amyloid deposits that target the osteo-articular system. The binding parameters of the interaction between collagen and beta2-m were determined by band shift electrophoresis and surface plasma resonance by using bovine collagen of type I and type II and various isoforms of beta2-m. Wild-type beta2-m binds collagen type I with a Kd of 4.1 x 10(-4) M and type II with 2.3 x 10(-3) M. By the BIAcore system we monitored the binding properties of the conformers of the slow phase of folding of beta2-m. The folding intermediates during the slow phase of folding do not display any significant difference with respect to the binding properties of the fully folded molecule. The affinity of beta2-m truncated at the third N-terminal residue does not differ from that reported for the wild-type protein. Increased affinity for collagen type I is found in the case of N-terminal truncated species lacking of six residues. The Kd of this species is 3.4 x 10 (-5) M at pH 7.4 and its affinity increases to 4.9 x 10(-6) M at pH 6.4. Fluctuations of the affinity caused by beta2-m truncation and pH change can cause modifications of protein concentration in the solvent that surrounds the collagen, and could contribute to generate locally a critical protein concentration able to prime the protein aggregation.
authors.affiliation: Dipartimento di Biochimica, Università degli Studi di Pavia, via Taramelli 3/b 27100 Pavia, Italy.
authors.forename: Sofia
authors.initials: S
authors.lastname: Giorgetti
authors.forename: Antonio
authors.initials: A
authors.lastname: Rossi
authors.forename: Palma
authors.initials: P
authors.lastname: Mangione
authors.forename: Sara
authors.initials: S
authors.lastname: Raimondi
authors.forename: Sara
authors.initials: S
authors.lastname: Marini
authors.forename: Monica
authors.initials: M
authors.lastname: Stoppini
authors.forename: Alessandra
authors.initials: A
authors.lastname: Corazza
authors.forename: Paolo
authors.initials: P
authors.lastname: Viglino
authors.forename: Gennaro
authors.initials: G
authors.lastname: Esposito
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Cetta
authors.forename: Giampaolo
authors.initials: G
authors.lastname: Merlini
authors.forename: Vittorio
authors.initials: V
authors.lastname: Bellotti
mesh_terms: D000686:Amyloidosis / Q000378:metabolism; D000818:Animals; D015374:Biosensing Techniques; D002417:Cattle; D024042:Collagen Type I / Q000378:metabolism*; D024043:Collagen Type II / Q000378:metabolism; D004587:Electrophoresis, Agar Gel; D009154:Mutation; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary; D013997:Time Factors; D001613:beta 2-Microglobulin / Q000235:genetics / Q000378:metabolism*
chemical_list: D024042:Collagen Type I; D024043:Collagen Type II; D020033:Protein Isoforms; D001613:beta 2-Microglobulin