Novel N-terminal mutation of human apolipoprotein A-I reduces self-association and impairs LCAT activation.

ABSTRACT: We have identified a novel mutation in apoA-I (serine 36 to alanine; S36A) in a human subject with severe hypoalphalipoproteinemia. The mutation is located in the N-terminal region of the protein, which has been implicated in several functions, including lipid binding and lecithin:cholesterol acyltransferase (LCAT) activity. In the present study, the S36A protein was produced recombinantly and characterized both structurally and functionally. While the helical content of the mutant protein was lower compared with wild-type (WT) apoA-I, it retained its helical character. The protein stability, measured as the resistance to guanidine-induced denaturation, decreased significantly. Interestingly, native gel electrophoresis, cross-linking, and sedimentation equilibrium analysis showed that the

SUBMITTER: Weers PM 

PROVIDER: S-EPMC2999918 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature