Molecular expression, characterization and mechanism of ALAS2 gain-of-function mutants.

ABSTRACT:

Background

X-linked protoporphyria (XLP) (MIM 300752) is an erythropoietic porphyria due to gain-of-function mutations in the last exon (Ducamp et al., Hum Mol Genet 22:1280-88, 2013) of the erythroid-specific aminolevulinate synthase gene (ALAS2). Five ALAS2 exon 11 variants identified by the NHBLI Exome sequencing project (p.R559H, p.E565D, p.R572C, p.S573F and p.Y586F) were expressed, purified and characterized in order to assess their possible contribution to XLP. To further characterize the XLP gain-of-function region, five novel ALAS2 truncation mutations (p.P561X, p.V562X, p.H563X, p.E569X and p.F575X) were also expressed and studied.

Methods

Site-directed mutagenesis was used to generate ALAS2 mutant clones and all were prokaryotically expressed, purified to near hom

SUBMITTER: Tchaikovskii V 

PROVIDER: S-EPMC6344999 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature