2005/04/02 by Xuewei Zhu, Gang Wu, Wuwei Zeng +2 · 33 citations
Biochemistry, Genetics and Molecular Biology · Chemistry · Medicine · #Apolipoprotein B #Biochemistry #Chemistry #Cholesterol #Cysteine #Diabetes, Cardiovascular Risks, and Lipoproteins #Efflux #Enzyme #Gene #Lipoproteins and Cardiovascular Health #Mutant #Peroxisome Proliferator-Activated Receptors #Protein secondary structure #Residue (chemistry)
paper · pdf · doi:10.1194/jlr.m400401-jlr200
published in Journal of Lipid Research 46(6), 1303-1311 (Elsevier BV)
openalex publication_date 2005/04/02 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/23
Apolipoprotein A-I(Milano) (A-I(M)) (R173C), a natural mutant of human apolipoprotein A-I (apoA-I), and five other cysteine variants of apoA-I at residues 52 (S52C), 74 (N74C), 107 (K107C), 129 (G129C), and 195 (K195C) were generated. Cysteine residues were incorporated in each of the various helices at the same helical wheel position as for the substitution in A-I(M). The secondary structural properties of the monomeric mutants, their abilities to bind lipid and to promote cholesterol efflux from THP-1 macrophages, and the possibility of antiperoxidation were investigated. Results showed that the alpha helical contents of all of the cysteine mutants were similar to that of wild-type apoA-I (wtapoA-I). The cysteine variant of A-I(M) at residue 173 [A-I(M)(R173C)] exhibited weakened structural stability, whereas A-I(G129C) a more stable structure than wtapoA-I. A-I(G129C) and A-I(K195C) exhibited significantly impaired capabilities to bind lipid compared with wtapoA-I. A-I(K107C) possessed a higher capacity to promote cholesterol efflux from macrophages than wtapoA-I, and A-I(M)(R173C) and A-I(K195C) exhibited an impaired efflux capability. Neither A-I(M)(R173C) nor any other cysteine mutant could resist oxidation against lipoxygenase. In summary, in spite of the similar mutant position on the helix, these variants exhibited different structural features or biological activities, suggesting the potential influence of the local environment of mutations on the whole polypeptide chain.