Human beta two microglobulin: Difference between revisions
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=Structure of human beta two microglobulin= | |||
==Beta two microglubulin in human class I major histocompatibility complex (MHCb2m)== | ==Beta two microglubulin in human class I major histocompatibility complex (MHCb2m)== | ||
Human β2-Microglobulin is the non-covalently bound light chain of | Human β2-Microglobulin is the non-covalently bound light chain of | ||
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Fig.2. Ribbon diagram showing the position of HIs-51 in the crystal structure of Mhb2m (left) and MHCb2m (right) | Fig.2. Ribbon diagram showing the position of HIs-51 in the crystal structure of Mhb2m (left) and MHCb2m (right) | ||
=Amyloid Fibril formation of Mhb2m= | |||
==Mhb2m fiber formation conditions== | |||
While the exact factors that cause b2m fibril formation in vivo are not known, several means exist to generate b2m amyloid fibrils in vitro. b2m amyloid fibrils can be generated under acidic conditions (pH < 3.6), by truncating the first six N-terminal amino | |||
acids, by dialyzing the protein into distilled water followed by membrane drying, by mixing the protein with collagen at pH=6.4, by sonicating the protein in the presence of sodium dodecyl sulfate at pH=7.0, and by incubating the full-length protein at | |||
physiological conditions in the presence of stoichiometric amounts of Cu(II).The latter method is particularly intriguing and may have relevance to the in vivo process because of the very near physiological conditions used. | |||
==Mhb2m fiber formation mechanism at neutral pH== | |||
===A structural trigger=== | |||
Alterations of the protein sequence have been used to stimulate the formation of fibrils at neutral pH. Specifically, truncation of six residues from the N-terminal region(DN6), as well as mutation in this region (P5G) or in the B/C or D/E loops (P32A, P32G, D59P) of the protein all enhance its ability to form amyloid in vitro (Fig.3), while substitutions elsewhere in the protein have little effect. These studies have the common feature that they encourage partial unfolding of b2m, allowing the aggregation-prone regions of the polypeptide sequence to be exposed and to participate in intermolecular interactions. | |||
