Structure, function and amyloidogenic propensity of apolipoprotein A-I.
Apolipoprotein A-I, the major structural apolipoprotein of high-density lipoproteins, efficiently protects humans from cholesterol accumulation in tissues; however, it can cause systemic amyloidosis in the presence of peculiar amino acid replacements. The wild-type molecule also has an intrinsic tendency to generate amyloid fibrils that localise within the atherosclerotic plaques. The structure, folding and metabolism of normal apolipoprotein A-I are extremely complex and as yet not completely clarified, but their understanding appears essential for the elucidation of the amyloid transition. We reviewed present knowledge on the structure, function and amyloidogenic propensity of apolipoprotein A-I with the aim of highlighting the possible molecular mechanisms that might contribute to the pathogenesis of this disease. Important clues on apolipoprotein A-I amyloidogenesis may be obtained from classical comparative studies of the properties of the wild-type versus the amyloidogenic counterpart. Additionally, in the case of apoA-I, further insights on the molecular mechanisms underlying its amyloidogenic propensity may derive from comparative studies between amyloidogenic variants and other mutations associated with hypoalphalipoproteinemia without amyloidosis.
Obici
Laura
L
Centro per lo Studio e la Cura delle Amiloidosi Sistemiche, Laboratorio di Biotecnologie, IRCCS Policlinico San Matteo, Pavia, Italy.
Franceschini
Guido
G
Calabresi
Laura
L
Giorgetti
Sofia
S
Stoppini
Monica
M
Merlini
Giampaolo
G
Bellotti
Vittorio
V
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000682:Amyloid / Q000502:physiology*; D016632:Apolipoprotein A-I / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D011487:Protein Conformation; D017510:Protein Folding
D000682:Amyloid; D016632:Apolipoprotein A-I