ABCMdb

PMID: 19258317

Hozoji M, Kimura Y, Kioka N, Ueda K
Formation of two intramolecular disulfide bonds is necessary for ApoA-I-dependent cholesterol efflux mediated by ABCA1.
J Biol Chem. 2009 Apr 24;284(17):11293-300. Epub 2009 Mar 3., [PubMed]

Sentences

No. Mutations Sentence Comment

25 ABCA1 p.Cys1477Arg ABCA4 p.Cys1488Arg ABCA4 p.Cys54Tyr ABCA4 p.Cys1490Tyr ABCA4 p.Cys75Gly Indeed, the Tangier disease mutation C1477R has been reported to abolish apoA-I binding and HDL formation (15-17), and several missense mutations in cysteine residues within ECD1 (C54Y, C75G) and ECD2 (C1488R, C1490Y) of ABCA4 have been linked to Stargardt * Thisworkwassupportedbyagrant-in-aidforscientificresearch(S)fromthe Ministry of Education, Culture, Sports, Science, and Technology of Japan, by the Program for Promotion of Fundamental Studies in Health Sciences of the National Institute of Biomedical Innovation, and by the World Premier International Research Center Initiative, Ministry of Education, Culture, Sports, Science, and Technology of Japan. Login to comment 88 ABCA1 p.Lys939Met ABCA1 p.Lys1952Met ApoA-I bound to cells expressing wild-type ABCA1 but not to cells expressing ABCA1-MM (ABCA1(K939M/K1952M)), a mutant in which the Walker A lysines in both nucleotide-binding domains are replaced by methionines, although the expression level (data not shown) and surface expression (Fig. 4A) of the mutant were comparable with those of the wild-type protein, as reported (24). Login to comment 90 ABCA1 p.Lys939Met ABCA1 p.Lys1952Met ApoA-I bound to cells expressing wild-type ABCA1 but not to cells expressing ABCA1-MM (ABCA1(K939M/K1952M)), a mutant in which the Walker A lysines in both nucleotide-binding domains are replaced by methionines, although the expression level (data not shown) and surface expression (Fig. 4A) of the mutant were comparable with those of the wild-type protein, as reported (24). Login to comment 122 ABCA1 p.Cys195Ser ABCA1 p.Cys195Ser ABCA1 p.Cys195Ser ABCA1 p.Cys195Ser ABCA1 p.Cys215Ser ABCA1 p.Cys215Ser ABCA1 p.Cys215Ser ABCA1 p.Cys215Ser ABCA1 p.Cys309Ser ABCA1 p.Cys309Ser ABCA1 p.Cys309Ser ABCA1 p.Cys355Ser ABCA1 p.Cys355Ser ABCA1 p.Cys355Ser ABCA1 p.Cys355Ser ABCA1 p.Cys81Ser ABCA1 p.Cys81Ser ABCA1 p.Cys81Ser ABCA1 p.Cys81Ser ABCA1 p.Cys54Ser ABCA1 p.Cys54Ser ABCA1 p.Cys54Ser ABCA1 p.Cys54Ser ABCA1 p.Cys791Ser ABCA1 p.Cys791Ser ABCA1 p.Cys791Ser ABCA1 p.Cys791Ser ABCA1 p.Cys1814Ser ABCA1 p.Cys1814Ser ABCA1 p.Cys626Ser ABCA1 p.Cys626Ser ABCA1 p.Cys626Ser ABCA1 p.Cys626Ser ABCA1 p.Cys1465Ser ABCA1 p.Cys1465Ser ABCA1 p.Cys1465Ser ABCA1 p.Cys1465Ser ABCA1 p.Cys1465Ser ABCA1 p.Cys1465Ser ABCA1 p.Cys1465Ser ABCA1 p.Cys1465Ser ABCA1 p.Cys1465Ser ABCA1 p.Cys1465Ser ABCA1 p.Cys75Ser ABCA1 p.Cys75Ser ABCA1 p.Cys75Ser ABCA1 p.Cys1418Ser ABCA1 p.Cys1418Ser ABCA1 p.Cys1418Ser ABCA1 p.Cys1418Ser ABCA1 p.Cys1418Ser ABCA1 p.Cys1418Ser ABCA1 p.Cys1418Ser ABCA1 p.Cys1418Ser ABCA1 p.Cys1418Ser ABCA1 p.Cys1418Ser ABCA1 p.Cys1429Ser ABCA1 p.Cys1429Ser ABCA1 p.Cys1429Ser ABCA1 p.Cys1429Ser ABCA1 p.Cys1429Ser ABCA1 p.Cys1429Ser ABCA1 p.Cys1429Ser ABCA1 p.Cys1429Ser ABCA1 p.Cys1429Ser ABCA1 p.Cys1429Ser ABCA1 p.Cys1477Ser ABCA1 p.Cys1477Ser ABCA1 p.Cys1477Ser ABCA1 p.Cys1477Ser ABCA1 p.Cys1477Ser ABCA1 p.Cys1477Ser ABCA1 p.Cys1477Ser ABCA1 p.Cys1477Ser ABCA1 p.Cys1463Ser ABCA1 p.Cys1463Ser ABCA1 p.Cys1463Ser ABCA1 p.Cys1463Ser ABCA1 p.Cys1463Ser ABCA1 p.Cys1463Ser ABCA1 p.Cys1463Ser ABCA1 p.Cys1463Ser ABCA1 p.Cys1463Ser ABCA1 p.Cys1463Ser ABCA1 p.Cys504Ser ABCA1 p.Cys504Ser ABCA1 p.Cys504Ser ABCA1 p.Cys504Ser TABLE 1 Cysteine mutants of ABCA1 Protein ApoA-I binding Cholesterol efflux Mutations Wild type af9; af9; None C1S af9; af9; C54S C2S afa; afa; C75S C3S af9; af9; C81S C4S af9; af9; C195S C5S af9; af9; C215S C6S afa; afa; C309S C7S af9; af9; C355S C8S af9; af9; C504S C9S af9; af9; C626S C10S af9; af9; C791S C11S af9; af9; C1418S C12S af9; af9; C1429S C13S af9; af9; C1463S C14S af9; af9; C1465S C15S af9; afa; C1477S C16S af9; af9; C1814S C2/6S afa; afa; C75S/C309S C11/12S af9; af9; C1418S/C1429S C13/14S afa; afa; C1463S/C1465S C13/14/15S afa; afa; C1463S/C1465S/C1477S C11/12/13/14S afa; afa; C1418S/C1429S/C1463S/C1465S C11/12/13/15S afa; afa; C1418S/C1429S/C1463S/C1477S C11/12/14/15S afa; afa; C1418S/C1429S/C1465S/C1477S C11/13/14/15S afa; afa; C1418S/C1463S/C1465S/C1477S C12/13/14/15S afa; afa; C1429S/C1463S/C1465S/C1477S C11/12/13/14/15S afa; afa; C1418S/C1429S/C1463S/C1465S/C1477S C2/6/13/14/15S afa; afa; C75S/C309S/C1463S/C1465S/C1477S Cys4#1 af9; af9; C54S/C81S/C195S/C215S/C355S/C504S/C626S/C791S/C1418S/C1429S/C1465S/1814S Cys4#2 af9; af9; C54S/C81S/C195S/C215S/C355S/C504S/C626S/C791S/C1418S/C1429S/C1463S/1814S Cys5 af9; af9; C54S/C81S/C195S/C215S/C355S/C504S/C626S/C791S/C1418S/C1429S/C1814S Two Intramolecular Disulfide Bonds in ABCA1 APRIL 24, 2009ߦVOLUME 284ߦNUMBER 17 JOURNAL OF BIOLOGICAL CHEMISTRY 11297 irreversibly abolished apoA-I binding to cells expressing ABCA1(Cys5)-GFP (supplemental Fig. 4). Login to comment 124 ABCA1 p.Cys195Ser ABCA1 p.Cys195Ser ABCA1 p.Cys195Ser ABCA1 p.Cys195Ser ABCB2 p.Cys12Ser ABCA1 p.Cys215Ser ABCA1 p.Cys215Ser ABCA1 p.Cys215Ser ABCA1 p.Cys215Ser ABCA1 p.Cys309Ser ABCA1 p.Cys309Ser ABCA1 p.Cys309Ser ABCA1 p.Cys355Ser ABCA1 p.Cys355Ser ABCA1 p.Cys355Ser ABCA1 p.Cys355Ser ABCA1 p.Cys81Ser ABCA1 p.Cys81Ser ABCA1 p.Cys81Ser ABCA1 p.Cys81Ser ABCA1 p.Cys54Ser ABCA1 p.Cys54Ser ABCA1 p.Cys54Ser ABCA1 p.Cys54Ser ABCA1 p.Cys791Ser ABCA1 p.Cys791Ser ABCA1 p.Cys791Ser ABCA1 p.Cys791Ser ABCA1 p.Cys1814Ser ABCA1 p.Cys1814Ser ABCA1 p.Cys626Ser ABCA1 p.Cys626Ser ABCA1 p.Cys626Ser ABCA1 p.Cys626Ser ABCA1 p.Cys1465Ser ABCA1 p.Cys1465Ser ABCA1 p.Cys1465Ser ABCA1 p.Cys1465Ser ABCA1 p.Cys1465Ser ABCA1 p.Cys1465Ser ABCA1 p.Cys1465Ser ABCA1 p.Cys1465Ser ABCA1 p.Cys1465Ser ABCA1 p.Cys1465Ser ABCA1 p.Cys75Ser ABCA1 p.Cys75Ser ABCA1 p.Cys75Ser ABCA1 p.Cys1418Ser ABCA1 p.Cys1418Ser ABCA1 p.Cys1418Ser ABCA1 p.Cys1418Ser ABCA1 p.Cys1418Ser ABCA1 p.Cys1418Ser ABCA1 p.Cys1418Ser ABCA1 p.Cys1418Ser ABCA1 p.Cys1418Ser ABCA1 p.Cys1418Ser ABCA1 p.Cys1429Ser ABCA1 p.Cys1429Ser ABCA1 p.Cys1429Ser ABCA1 p.Cys1429Ser ABCA1 p.Cys1429Ser ABCA1 p.Cys1429Ser ABCA1 p.Cys1429Ser ABCA1 p.Cys1429Ser ABCA1 p.Cys1429Ser ABCA1 p.Cys1429Ser ABCA1 p.Cys1477Ser ABCA1 p.Cys1477Ser ABCA1 p.Cys1477Ser ABCA1 p.Cys1477Ser ABCA1 p.Cys1477Ser ABCA1 p.Cys1477Ser ABCA1 p.Cys1477Ser ABCA1 p.Cys1477Ser ABCA1 p.Cys1463Ser ABCA1 p.Cys1463Ser ABCA1 p.Cys1463Ser ABCA1 p.Cys1463Ser ABCA1 p.Cys1463Ser ABCA1 p.Cys1463Ser ABCA1 p.Cys1463Ser ABCA1 p.Cys1463Ser ABCA1 p.Cys1463Ser ABCA1 p.Cys1463Ser ABCA1 p.Cys504Ser ABCA1 p.Cys504Ser ABCA1 p.Cys504Ser ABCA1 p.Cys504Ser TABLE 1 Cysteine mutants of ABCA1 Protein ApoA-I binding Cholesterol efflux Mutations Wild type ϩ ϩ None C1S ϩ ϩ C54S C2S - - C75S C3S ϩ ϩ C81S C4S ϩ ϩ C195S C5S ϩ ϩ C215S C6S - - C309S C7S ϩ ϩ C355S C8S ϩ ϩ C504S C9S ϩ ϩ C626S C10S ϩ ϩ C791S C11S ϩ ϩ C1418S C12S ϩ ϩ C1429S C13S ϩ ϩ C1463S C14S ϩ ϩ C1465S C15S ϩ - C1477S C16S ϩ ϩ C1814S C2/6S - - C75S/C309S C11/12S ϩ ϩ C1418S/C1429S C13/14S - - C1463S/C1465S C13/14/15S - - C1463S/C1465S/C1477S C11/12/13/14S - - C1418S/C1429S/C1463S/C1465S C11/12/13/15S - - C1418S/C1429S/C1463S/C1477S C11/12/14/15S - - C1418S/C1429S/C1465S/C1477S C11/13/14/15S - - C1418S/C1463S/C1465S/C1477S C12/13/14/15S - - C1429S/C1463S/C1465S/C1477S C11/12/13/14/15S - - C1418S/C1429S/C1463S/C1465S/C1477S C2/6/13/14/15S - - C75S/C309S/C1463S/C1465S/C1477S Cys4#1 ϩ ϩ C54S/C81S/C195S/C215S/C355S/C504S/C626S/C791S/C1418S/C1429S/C1465S/1814S Cys4#2 ϩ ϩ C54S/C81S/C195S/C215S/C355S/C504S/C626S/C791S/C1418S/C1429S/C1463S/1814S Cys5 ϩ ϩ C54S/C81S/C195S/C215S/C355S/C504S/C626S/C791S/C1418S/C1429S/C1814S irreversibly abolished apoA-I binding to cells expressing ABCA1(Cys5)-GFP (supplemental Fig. 4). Login to comment 173 ABCA4 p.Cys1488Arg ABCA4 p.Cys1490Tyr C13 and C14 are conserved among ABCA1, ABCA4, and ABCA7, and mutations of both C13 (C1488R) and C14 (C1490Y) of ABCA4 are linked to Stargardt disease (20), suggesting that these two cysteines are functionally important and cannot substitute for each other in ABCA4. Login to comment 175 ABCA4 p.Cys1488Arg ABCA4 p.Cys1490Tyr C13 and C14 are conserved among ABCA1, ABCA4, and ABCA7, and mutations of both C13 (C1488R) and C14 (C1490Y) of ABCA4 are linked to Stargardt disease (20), suggesting that these two cysteines are functionally important and cannot substitute for each other in ABCA4. Login to comment 190 ABCA1 p.Trp590Ser The Tangier mutation W590S impairs apoA-I-dependent cholesterol efflux but not apoA-I binding (15). Login to comment 191 ABCA1 p.Trp590Ser The replacement of C15 by serine may cause conformational changes similar to those caused by the W590S mutation. Login to comment 192 ABCA1 p.Trp590Ser The Tangier mutation W590S impairs apoA-I-dependent cholesterol efflux but not apoA-I binding (15). Login to comment 193 ABCA1 p.Trp590Ser The replacement of C15 by serine may cause conformational changes similar to those caused by the W590S mutation. Login to comment