ABCMdb

PMID: 16501936

Zannis VI, Chroni A, Krieger M
Role of apoA-I, ABCA1, LCAT, and SR-BI in the biogenesis of HDL.
J Mol Med (Berl). 2006 Apr;84(4):276-94. Epub 2006 Feb 25., [PubMed]

Sentences

No. Mutations Sentence Comment

110 ABCA1 p.Leu144Arg ABCA1 p.Leu144Arg Another study suggested that phosphorylation of Thr-1286 and Thr-1305 within a proline, glutamic acid, serine, and threonine-rich domain (PEST) of ABCA1 promoted the calpain-mediated degradation in differentiated THP-1 cells and that binding of apoA-I to ABCA1 promoted dephos- 509 13 65 67 98 100 120 122 142 144 164 184 219 242166 186 22887 208 12 34 5 6 7 8,91 0 Leu90Pro ∆Lys107 Pr ApoA-I mutations associated with reduced LCAT activation and/or low HDL levels COOHNH2 509 13 65 67 98 100 120 122 142 144 164 184 219 242166 186 22887 208 1 2 3 4 5 6 7 8,9 10 Gly26Arg Trp50Arg Leu60Arg ∆(60-71), INS Val, Thr ∆(70-72) Arg173Pro ∆Lys107 Leu141Arg Pro143Arg ∆Glu235 FS 203-229, ∆(230-243), Arg173Cys ∆(165-175) o165Arg FS 162-207, ∆(208-243) Arg160Leu Leu159Arg Leu159Pro Ala158Glu Val156Glu Arg151Cys ∆(146-160) Leu144Arg ApoA-I mutations associated with reduced LCAT activation and/or low HDL levels ApoA-I mutations associated with familial amyloidosis and low HDL levels b Fig. 2 (continued) phorylation and decreased its degradation [57]. Login to comment 147 ABCA1 p.Trp590Ser ABCA1 p.Gln597Arg ABCA1 p.Cys1477Arg ABCA1 p.Arg587Trp ABCA1 p.Ser1506Leu In vitro analysis of the effects on apoA-I/ABCA1 interactions (cross-linking assay) by mutations in ABCA1 that are found in Tangier disease patients and diminish lipid efflux [71] showed that cross-linking was dramatically reduced to 5-10% of the WT control for three mutants (Gln597Arg, Cys1477Arg, and Ser1506Leu), reduced by 50% for the Arg587Trp mutant, and was remarkably increased to 125% of control for the Trp590Ser mutant [71]. Login to comment 148 ABCA1 p.Trp590Ser ABCA1 p.Trp590Ser Additional analysis of interactions of the mutant forms of apoA-I with the Trp590Ser mutant raised the possibility that the Trp590Ser mutation may have altered the environment in the binding site of ABCA1 in a way that prevented efficient lipid efflux despite the increased binding [73]. Login to comment 163 ABCA1 p.Trp590Ser ApoA-I/ABCA1 binding, which exhibits a half-life of approximately 30 min [77], appears to be a necessary but not sufficient step for lipid efflux (see description of the Trp590Ser mutant above) [33, 34, 71, 80]. Login to comment 165 ABCA1 p.Trp590Ser This appears to require the formation of a productive complex between apoA-I and ABCA1 because in the case of the ABCA1 [Trp590Ser] mutant that is associated with Tangier disease [31, 32, 71], an apoA1/ABCA1 complex is formed but the apoA-I is not lipidated and is subsequently released in a lipid-free form [77]. Login to comment 264 ABCA1 p.Trp590Ser For instance, the binding of WT apoA-I to ABCA1[Trp590Ser] may not be productive and as a consequence, results in defective lipid efflux. Login to comment