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

Abstract

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.