ABCG1 p.Tyr649Leu
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PMID: 25732853
[PubMed]
Sharpe LJ et al: "Cholesterol sensing by the ABCG1 lipid transporter: Requirement of a CRAC motif in the final transmembrane domain."
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Comment
147
Individual point mutations of Y649L, Y667L and Y672L were introduced into ABCG1 and stable cell lines overexpressing the individual mutants generated.
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ABCG1 p.Tyr649Leu 25732853:147:30
status: NEW148 Fig. 3A shows that the activity of both the Y649L and Y667L mutants was totally abolished, while the Y672L mutant had reduced cholesterol export activity (this latter difference was not statistically significant).
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ABCG1 p.Tyr649Leu 25732853:148:44
status: NEW151 The Y649L and Y672L mutant proteins however, were consistently stabilised by the addition of cholesterol, suggesting that their cholesterol "sensing" ability was still intact, despite having reduced or negligible cholesterol export capacity.
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ABCG1 p.Tyr649Leu 25732853:151:4
status: NEW163 This may explain why the Y649L mutation inhibited the cholesterol transport activity of ABCG1 without affecting its stabilisation by cholesterol.
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ABCG1 p.Tyr649Leu 25732853:163:25
status: NEW174 2A) Cholesterol export of parental CHOK1 cells (CHOK1), CHOK1 cells overexpressing wild-type ABCG1 (ABCG1), or two independent clones overexpressing triple Y649L, Y667L and Y672L mutants (Triple Y/L).
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ABCG1 p.Tyr649Leu 25732853:174:156
status: NEW203 3A) Cholesterol export of CHOK1 cells overexpressing ABCG1 with a single mutation (Y649L, Y667L or Y672L).
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ABCG1 p.Tyr649Leu 25732853:203:83
status: NEW205 Statistically significant differences in HDL-mediated export (via 2-way ANOVA; p b 0.05) are indicated between cells overexpressing ABCG1 vs CHOK1, Y649L and Y667L mutants.
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ABCG1 p.Tyr649Leu 25732853:205:148
status: NEW