Effects of the Iowa and Milano mutations on apolipoprotein A-I structure and dynamics determined by hydrogen exchange and mass spectrometry.

ABSTRACT: The Iowa point mutation in apolipoprotein A-I (G26R) leads to a systemic amyloidosis condition, and the Milano mutation (R173C) is associated with hypoalphalipoproteinemia, a reduced plasma level of high-density lipoprotein. To probe the structural effects that lead to these outcomes, we used amide hydrogen-deuterium exchange coupled with a fragment separation/mass spectrometry analysis (HX MS). The Iowa mutation inserts an arginine residue into the nonpolar face of an α-helix that spans residues 7-44 and causes changes in structure and structural dynamics. This helix unfolds, and other helices in the N-terminal helix bundle domain are destabilized. The segment encompassing residues 116-158, largely unstructured in wild-type apolipoprotein A-I, becomes helical. The helix spanning residues

SUBMITTER: Chetty PS 

PROVIDER: S-EPMC3493162 | biostudies-literature | 2012 Nov

REPOSITORIES: biostudies-literature