Structural and Thermodynamic Characteristics of Amyloidogenic Intermediates of β-2-Microglobulin.

ABSTRACT: β-2-microglobulin (β2m) self-aggregates to form amyloid fibril in renal patients taking long-term dialysis treatment. Despite the extensive structural and mutation studies carried out so far, the molecular details on the factors that dictate amyloidogenic potential of β2m remain elusive. Here we report molecular dynamics simulations followed by the solvation thermodynamic analyses on the wild-type β2m and D76N, D59P, and W60C mutants at the native (N) and so-called aggregation-prone intermediate (IT) states, which are distinguished by the native cis- and non-native trans-Pro32 backbone conformations. Three major structural and thermodynamic characteristics of the IT-state relative to the N-state in β2m protein are detected that contribute to the increased amyloidogenic potential: (i) the d

SUBMITTER: Chong SH 

PROVIDER: S-EPMC4562173 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature