Human beta two microglobulin
From Proteopedia
Beta two microglubulin in human class I major histocompatibility complex (MHCb2m)
Human β2-Microglobulin is the non-covalently bound light chain of the human class I major histocompatibility complex (MHC-I). its function is to ensure proper folding and cell-surface expression of MHC-1. The natural turnover of MHC-I gives rise to the release of b2m into plasmatic fluids at ~0.1 um and to its catabolism in the kidney. In case of renal dysfunction, b2m concentration increases up to 60-fold, giving rise to pathogenic accumulation of filamentous structures, displaying the typical properties of amyloid fibrils, principally in the joints and connective tissue.
Monomeric human b2m (Mhb2m)
The first crystal structure of monomeric human b2m (Mhb2m) is solved in 2002. The protein is 99 residue in length and has a seven-stranded β sandwich fold typical of the Immunoglobulin superfamily. It is stabilized by a single disulfide bond between Cys-25 and Cys-80, which links the two β sheets.
Structural comparison of MHCb2m and Mhb2m
Image:Human b2m bound to MHC-1 .jpg.jpg Image:Momeric human b2m.png
Fig.1. crystal structures of MHCb2m (left)and Mhb2m (right)
Both of the two strucures adopt seven-stranded β sandwich fold. The most significant difference in the ctrystal structures of Mhb2m and MHCb2m involves residues in β strand D and the succeeding loop. When complexed with the MHC heavy chain, residues 50-56 of MHCb2m form two short β strands that separated by a two residue β bulge. These strands (depicted as D1 and D2 in Fig.1) each forms three main-chain-main-chain hydrogen bonds to the adjacent β strand E. The bulge in MHCb2m effectively twists the edge strand, which facilitate its binding to the surface of the heavy chain. However, this β bulge no longer exits in the crytal strucure of Mhb2m. The conformation of D strand in Mhb2m provides an ideal assembly surface, making this edge-strand pair vulnerable to aggregation. The hydrogen-bonding potential of strand D is satisfied by the formation intermolecular interactionswith adjecent molecules, demonstrating the potential for this region to propagate assembly through edge-strand interactions.
In addition, the changes observed in strand D result in differenr orientations of the side chains of residues 50-54. As a result, His-51 (which points inwards in the structure of MHCb2m) rotates by approximately 180, such that it now points away from the hydrophobic core of the protein. This would remove the second protevtive feature from the edge strand, facilitating further interaction in this region.
Fig.2. Ribbon diagram showing the position of HIs-51 in the crystal structure of Mhb2m (left) and MHCb2m (right)
