β2-Microglobulin isoforms display an heterogeneous affinity for type I collagen

It has been claimed that β2-microglobulin (β2-m) interacts with type I and type II collagen, and this property has been linked to the tissue specificity of the β2-m amyloid deposits that target the osteo-articular system. The binding parameters of the interaction between collagen and β2-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 β2-m. Wild-type β2-m binds collagen type I with a K_d of 4.1 × 10^-4 M and type II with 2.3 × 10^-3 M. By the BIAcore system we monitored the binding properties of the conformers of the slow phase of folding of β2-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 β2-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 K_d of this species is 3.4 × 10^-5 M at pH 7.4 and its affinity increases to 4.9 × 10^-6 M at pH 6.4. Fluctuations of the affinity caused by β2-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.