ABCMdb

ABCA1 p.Leu2247Ala

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Publications

PMID: 21507939 [PubMed] Hozoji-Inada M et al: "Liver X receptor beta (LXRbeta) interacts directly with ATP-binding cassette A1 (ABCA1) to promote high density lipoprotein formation during acute cholesterol accumulation."

No. Sentence Comment

90 However, mutation of Leu2247 and Leu2251 to alanine abrogated the co-precipitation of LXRbeta despite comparable levels of expression among these mutants and WT ABCA1. Login to comment
108 HEK293 cells stably expressing FLAG-tagged LXRbeta were transfected with HA-tagged WT ABCA1 L2247A mutant or L2251A mutant. Login to comment
113 When the mutant constructs were expressed in HEK293 cells, L2247A or L2251A substitution did not affect the surface expression of ABCA1, but LXRbeta no longer co-localized with ABCA1 (Fig. 2). Login to comment
120 Interestingly, apoA-I bound to cells expressing L2247A or L2251A mutant ABCA1 even when LXRbeta was co-expressed. Login to comment
122 When ABCA1-L2247A, ABCA1-L2251A, or ABCA1-L2247A/L2251A was expressed alone, cholesterol efflux to apoA-I was comparable with cells expressing WT ABCA1 in the absence or presence of TO901317 (black bars and empty bars, respectively, in Fig. 3B). Login to comment
126 Co-expression of LXRbeta doubled the plasma membrane levels of WT ABCA1 as shown previously (16), but surface levels of the mutants (L2247A, L2251A, and L2247/L2251A) were not affected by LXRbeta expression (Fig. 3C). Login to comment
149 ABCA1-L2247A/L2251A double mutant was labeled as efficiently as WT ABCA1 (lane 9), but this was not inhibited by LXRbeta co-expression (lanes 11 and 12), suggesting that the interaction of LXRbeta with ABCA1 via Leu2247 and Leu2251 prevents tight ATP binding. Login to comment
89 However, mutation of Leu2247 and Leu2251 to alanine abrogated the co-precipitation of LXRbeta despite comparable levels of expression among these mutants and WT ABCA1. Login to comment
107 HEK293 cells stably expressing FLAG-tagged LXRbeta were transfected with HA-tagged WT ABCA1 L2247A mutant or L2251A mutant. Login to comment
112 When the mutant constructs were expressed in HEK293 cells, L2247A or L2251A substitution did not affect the surface expression of ABCA1, but LXRbeta no longer co-localized with ABCA1 (Fig. 2). Login to comment
119 Interestingly, apoA-I bound to cells expressing L2247A or L2251A mutant ABCA1 even when LXRbeta was co-expressed. Login to comment
121 When ABCA1-L2247A, ABCA1-L2251A, or ABCA1-L2247A/L2251A was expressed alone, cholesterol efflux to apoA-I was comparable with cells expressing WT ABCA1 in the absence or presence of TO901317 (black bars and empty bars, respectively, in Fig. 3B). Login to comment
125 Co-expression of LXRbeta doubled the plasma membrane levels of WT ABCA1 as shown previously (16), but surface levels of the mutants (L2247A, L2251A, and L2247/L2251A) were not affected by LXRbeta expression (Fig. 3C). Login to comment
148 ABCA1-L2247A/L2251A double mutant was labeled as efficiently as WT ABCA1 (lane 9), but this was not inhibited by LXRbeta co-expression (lanes 11 and 12), suggesting that the interaction of LXRbeta with ABCA1 via Leu2247 and Leu2251 prevents tight ATP binding. Login to comment

PMID: 18782758 [PubMed] Hozoji M et al: "Direct interaction of nuclear liver X receptor-beta with ABCA1 modulates cholesterol efflux."

No. Sentence Comment

192 The coexpression of LXRbeta did not retard the degradation of ABCA1(L2247A), whereas the coexpression of ␣1-syntrophin retarded the degradation of ABCA1(L2247A) (supplemental Fig. 3, b and c). Login to comment
193 These results suggest that the amino acid substitution L2247A does not alter total protein conformation but rather specifically affects the interaction with LXRbeta. Login to comment
194 ABCA1(L2247A) showed significant apoA-I-dependent cholesterol efflux, and the addition of TO901317 did not affect it even when LXRbeta was coexpressed (supplemental Fig. 3d). Login to comment
191 The coexpression of LXRbeta did not retard the degradation of ABCA1(L2247A), whereas the coexpression of ॷ1-syntrophin retarded the degradation of ABCA1(L2247A) (supplemental Fig. 3, b and c). Login to comment