Human beta two microglobulin: Difference between revisions
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Similarities between the assembly mechanisms are supported by several | Similarities between the assembly mechanisms are supported by several reasons： | ||
1. the proposal that aromatic interactions are crucial for driving fibrillogenesis under both sets of conditions. | |||
2. Another convergent feature arises from a suggested model for the fibrils formed at neutral pH that contains a highly charged surface, which could be neutralised at low pH, perhaps allowing for a convergence of the mechanisms of assembly at acidic and neutral pH and explaining why the kinetics of fibril formation are much more rapid under acidic conditions. | '''1'''. the proposal that aromatic interactions are crucial for driving fibrillogenesis under both sets of conditions. | ||
3.An additional common characteristic is that many variants capable of fibril formation at neutral pH have the effect of destabilising the Nterminal region of the protein, which is also highly unfolded in the structural ensembles formed at low pH. | '''2'''. Another convergent feature arises from a suggested model for the fibrils formed at neutral pH that contains a highly charged surface, which could be neutralised at low pH, perhaps allowing for a convergence of the mechanisms of assembly at acidic and neutral pH and explaining why the kinetics of fibril formation are much more rapid under acidic conditions. | ||
4. The role of trans Pro32 in fibril formation at low pH is currently unknown, although 80% of the molecules would be expected to contain the trans conformation in the acid denatured state. Moreover, the observation that the rate of fibril formation of P32G is similar to that of wild-type b2m when studied at pH 2.5 is suggestive of a common trans amyloid precursor. | '''3'''.An additional common characteristic is that many variants capable of fibril formation at neutral pH have the effect of destabilising the Nterminal region of the protein, which is also highly unfolded in the structural ensembles formed at low pH. | ||
'''4'''. The role of trans Pro32 in fibril formation at low pH is currently unknown, although 80% of the molecules would be expected to contain the trans conformation in the acid denatured state. Moreover, the observation that the rate of fibril formation of P32G is similar to that of wild-type b2m when studied at pH 2.5 is suggestive of a common trans amyloid precursor. | |||
