Molecular playground/beta 2 microglobulin: Difference between revisions
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One hypothesis has emerged that the cis-trans isomerization of Pro32 is critical to the aggregation process. The <scene name='38/389965/141211_p32a/3'>P32A</scene> mutant has proved to be useful in this regard. With the Ala in the trans position, copper binding is enhanced 10,000 fold and has similar oligomerization kinetics to that of wild type-β2m. However, the structural effects of the mutation lead to an alternative dimer structure <ref>3</ref>. Seen here as a tetramer, it appears that the oligomer adopts a intermolecular β-sheet structure which is a hallmark of amyloids. | One hypothesis has emerged that the cis-trans isomerization of Pro32 is critical to the aggregation process. The <scene name='38/389965/141211_p32a/3'>P32A</scene> mutant has proved to be useful in this regard. With the Ala in the trans position, copper binding is enhanced 10,000 fold and has similar oligomerization kinetics to that of wild type-β2m. However, the structural effects of the mutation lead to an alternative dimer structure <ref>3</ref>. Seen here as a tetramer, it appears that the oligomer adopts a intermolecular β-sheet structure which is a hallmark of amyloids. | ||
The critical residue for copper binding, H31, has also been investigated. By mutating His31 to a Tyr, the positive charge is neutralized and the local environment | The critical residue for copper binding, H31, has also been investigated. By mutating His31 to a Tyr, the positive charge is neutralized and the local environment is minimally perturbed. Indeed, the H31Y mutant has increased stability relative to wild type and has reduced copper binding characteristics <ref>4</ref>. | ||
==Additional Resources== | ==Additional Resources== | ||
