ライフサイエンスコーパス: flippase

1 e action of inward-directed P-type ATPases ("flippases").

2 potential aminophospholipid translocase (or flippase).

3 re proposed to be phospholipid translocases (flippases).

4 s facilitated by specific membrane proteins (flippases).

5 l as a biochemical basis for identifying MPD flippase.

6 teraction between the DLO head group and the flippase.

7 herichia coli mviN gene encodes the lipid II flippase.

8 uted by LpxL are not good substrates for the flippase.

9 lated lipid A, which is optimal for the MsbA flippase.

10 ions in ATP8B1, a putative aminophospholipid flippase.

11 at are in agreement with a role of MurJ as a flippase.

12 e function of Atp8b1 as an aminophospholipid flippase.

13 biochemical means of identifying the M5-DLO flippase.

14 result indicates that Rft1 is not the M5-DLO flippase.

15 s of an undecaprenyl phosphate-alpha-L-Ara4N flippase.

16 ubstrate binding site of the plasma membrane flippase.

17 crease recognition by the plasma membrane PS flippase.

18 ry is maintained by the ATP-dependent enzyme flippase.

19 PS is maintained by the ATP-requiring enzyme flippase.

20 nhibitor of the endogenous aminophospholipid flippase.

21 scribe paves the way for identification of a flippase.

22 has been identified as a phosphatidylcholine flippase.

23 g for the existence of an alternate lipid II flippase.

24 CDC50A, and function as a phosphatidylserine flippase.

25 inner membrane protein MurJ is the lipid II flippase.

26 cient for the P4-ATPase Drs2, the primary PS flippase.

27 process facilitated by specific proteins or flippases.

28 r structural characterization of other lipid flippases.

29 is the founding member of a novel family of flippases.

30 rotein could function as phospholipid-GlcCer flippases.

31 hemical characteristics consistent with a PS flippase, a murine homologue of this enzyme was expresse

32 Mutations in the photoreceptor-specific flippase ABCA4 are associated with Stargardt disease and

33 nd that Dnf1, Dnf2, and Dnf3, as well as the flippase-activating protein kinase Fpk1, localize at the

34 pk1 is another protein kinase, Fpk1, a known flippase activator.

35 c fibroblasts (MEFs) exhibited diminished PS flippase activity and increased exposure of PS on the ce

36 egulate its own trafficking, suggesting that flippase activity and localization are linked.

37 lved it from both the ER glycerophospholipid flippase activity and the genetically identified flippas

38 We developed an assay for lipid II flippase activity and used a chemical genetic strategy t

39 y on Cibacron Blue dye resin enriched M5-DLO flippase activity approximately 5-fold and resolved it f

40 Here we show that MPD-flippase activity can be reconstituted in large unilamel

41 reliminary purification steps indicated that flippase activity could be enriched approximately 15-fol

42 Flippase activity depends on a critical cysteine residue

43 However, a flippase activity has not been reconstituted with purifi

44 o difference was seen in the level of M5-DLO flippase activity in sealed wild type and Rft1-depleted

45 Triton extract; and (iv) glycerophospholipid flippase activity in the ER can be attributed to two fun

46 k mechanism in which appropriately regulated flippase activity in the Golgi complex helps establish a

47 s of the N-ethylmaleimide-sensitive class of flippase activity revealed that the functionally critica

48 udies by describing two convenient assays of flippase activity utilizing fluorescent phospholipid ana

49 This flippase activity was mediated by Drs2p, because protein

50 terminally TAP-tagged Drs2p, both ATPase and flippase activity were significantly higher in the prese

51 e for the first time the reconstitution of a flippase activity with a purified P4-ATPase.

52 e is no evidence that Arfs directly regulate flippase activity, an Arf-guanine-nucleotide-exchange fa

53 ependent ATPase activity, phosphatidylserine flippase activity, and neurite extension in PC12 cells.

54 iched fraction devoid of glycerophospholipid flippase activity, we now report that M5-DLO is rapidly

55 ent-solubilized ER proteins were enriched in flippase activity, whereas others were inactive.

56 (2+) might not be the sole cause for loss of flippase activity.

57 no acid substitution known to inactivate the flippase activity.

58 relieved by a phosphoinositide to stimulate flippase activity.

59 nt N-glycosylation, indicating robust M5-DLO flippase activity.

60 lity of the complex and is indispensable for flippase activity.

61 P(4)-ATPases alone are sufficient to mediate flippase activity.

62 ect tests showed that these proteins have no flippase activity.

63 with CDC50A and displayed phosphatidylserine flippase activity.

64 inactivates Drs2p phospholipid translocase (flippase) activity disrupts its own transport in this AP

65 s2-dependent phosphatidylserine translocase (flippase) activity is hyperactive in TGN membranes from

66 Neo1 is thought to be a phospholipid flippase, although there is currently no experimental ev

67 yticus and include genes encoding a putative flippase, an aminotransferase, two glycosyltransferases,

68 Both flippase and Atp8a1 activities are insensitive to the st

69 revealed that PDI affects both the apparent flippase and floppase activities on endothelial cells.

70 membrane phospholipid translocation enzymes flippase and floppase, capon, NLRP3, and ASC.

71 idylethanolamine (PE) are substrates for the flippase and that other phospholipids move across the me

72 of results indicated that the wzx (O-antigen flippase) and wzy (O-antigen polymerase) genes were E. c

73 d organization, aminophospholipid transport (flippase), and prothrombin converting activity.

74 ain synthesis, the putative Wzx transporter (flippase), and the putative Wzy polymerase, respectively

75 e Golgi apparatus, lipid-synthesizing, lipid-flippase, and lipid-transport proteins (LTPs) collaborat

76 Lsg encodes a putative Wzx flippase, and mutation of Lsg affects only LPS; this fin

77 -phosphate (PI4P), a regulator of this lipid flippase, and specific to a phosphatidylserine substrate

78 , except that specific transport proteins or flippases are required.

79 Specific ER membrane proteins, flippases, are proposed to facilitate lipid flip-flop, b

80 P4-ATPases, also known as phospholipid flippases, are responsible for creating and maintaining

81 is presumed that specific membrane proteins, flippases, are responsible for phospholipid flip-flop.

82 of the undecaprenyl phosphate aminoarabinose flippase arnE/F genes from Escherichia coli.

83 which is transported by the plasma membrane flippase at a rate equivalent to PS, is incapable of act

84 Here, we establish that MmpL3 is the MA flippase at the IM of mycobacteria and is the molecular

85 mice lacking the putative phosphatidylserine flippase ATP11C showed a lower rate of PS translocation

86 A candidate PS flippase ATP8A1 (ATPase II), originally isolated from bo

87 Here we show that the disease-associated flippase ATPase class I type 8b member 1 (ATP8B1) enable

88 netic analyses implicated Rft1 as the M5-DLO flippase, but because biochemical tests challenged this

89 ane enzyme aminophospholipid-translocase (or flippase) by HNE and acrolein.

90 eover, we found that FtsW, but not the other flippase candidate MurJ, impairs lipid II polymerization

91 pase activity and the genetically identified flippase candidate Rft1.

92 , which encodes the canalicular phospholipid flippase, cause a wide spectrum of cholangiopathy phenot

93 pecifically abrogates PS recognition by this flippase causing PS exposure on the outer leaflet of the

94 However, for flippase-containing proteoliposomes, the initial rapid h

95 yeast type IV P-type ATPase (P4-ATPase), or flippase, couples ATP hydrolysis to phosphatidylserine t

96 blase complexes as well as ATP-dependence of flippases, data analysis in its context has remained a t

97 therefore, therefore, developed Flip-Flop, a flippase-dependent in vivo cassette-inversion method tha

98 Yeast S. cerevisiae has five flippases (Dnf1, Dnf2, Dnf3, Drs2, and Neo1), but their

99 kers SlaB(End4) and SagA(End3) and the lipid flippases DnfA and DnfB in the sub-apical collar region

100 h are not transported by the plasma membrane flippase, do not activate Atp8a1.

101 lytic domain and an N-terminal transmembrane flippase domain.

102 we show that the ATP-dependent phospholipid flippase Drs2 is required for efficient segregation of c

103 Two yeast flippases, Drs2 and Neo1, have nonredundant functions in

104 hydrolysis and auto-inhibition of the yeast flippase Drs2p-Cdc50p.

105 to bind to and stimulate the activity of the flippase Drs2p.

106 ow that (i) proteoliposomes generated from a flippase-enriched Triton X-100 extract of ER can flip an

107 : a collection of enhancer-trap recombinase, Flippase (ET-FLP), transgenic lines that provide inherit

108 spermatozoa; it is about 62% similar to the flippase, FIC1.

109 We developed new Flippase (FLP) reagents using proneural gene promoters t

110 integration, a helper plasmid expressing the flippase (FLP) recombinase allows precise in vivo excisi

111 vating sequence (UAS) binary system with the Flippase (FLP) recombination technique, we were able to

112 suggest that activation of the Drs2p-Cdc50p flippase follows a multistep mechanism, with preliminary

113 y overexpression of MsbA, the inner membrane flippase for core-lipid A.

114 that RmP functions as an outwardly directed flippase for N-retinylidene-PE.

115 published x-ray structure of MsbA, a lipid A flippase from Escherichia coli with high sequence homolo

116 ducible dual-recombinase system by combining flippase-FRT (Flp-FRT) and Cre-loxP recombination techno

117 Moreover, we found that decreasing flippase function rescued the growth deficiency of four

118 therefore an indirect negative regulator of flippase function.

119 c strategy to rapidly and specifically block flippase function.

120 sed to facilitate lipid flip-flop, but no ER flippase has been biochemically identified.

121 e erythrocyte membrane and suggests that the flippase has broader specificity for substrates or that

122 Although the flippase has not been positively identified, a subfamily

123 Although a phospholipid flippase has yet to be identified, evidence supporting t

124 No biogenic membrane flippases have been identified and there is controversy

125 Lipid translocases (flippases) have been implicated in vesicle formation thr

126 HfsF is predicted to be a flippase, HfsG is a glycosyltransferase, and HfsH is sim

127 e prior to reconstitution indicated that MPD flippase (i) is not a Con A-binding glycoprotein and (ii

128 ability of the DLO to be translocated by the flippase, (ii) glycan size per se does not dictate wheth

129 ification of an ATP-independent phospholipid flippase in any system.

130 as been proposed to function as the lipid II flippase in E. coli.

131 as a likely candidate for the peptidoglycan flippase in Escherichia coli.

132 hes to demonstrate that MurJ is the lipid II flippase in Escherichia coli.

133 ipped to the non-cytoplasmic face by a lipid flippase in order to nucleate glycosphingolipid synthesi

134 an inhibitor of the wall teichoic acid (WTA) flippase in Staphylococcus aureus.

135 Phospholipid flippases in the type IV P-type ATPase (P4-ATPases) fami

136 ng that they likely do not serve as lipid II flippases in this organism.

137 and potential aminophospholipid translocase (flippase) in the Drs2p family.

138 Two of the P-type ATPases (flippases) in yeast, Dnf1 and Dnf2, translocate aminogly

139 ion for ATP11C, a putative aminophospholipid flippase, in B cell development.

140 -type ATPases, and it is unknown whether the flippases interact directly with the lipid and with coun

141 whether a DLO will be flipped, and (iii) the flippase is highly specific for M5-DLO.

142 ylated in LpxM mutants by LpxF when the MsbA flippase is inactivated, indicating that LpxF faces the

143 e, in a purified system, that a phospholipid flippase is subject to auto-inhibition by its C-terminal

144 ecular identity of the MPD translocator (MPD flippase) is not known.

145 coli MsbA, the proposed inner membrane lipid flippase, is an essential ATP-binding cassette transport

146 -Dol in vivo, but the Man(5)GlcNAc(2)-PP-Dol flippase itself remains to be identified.

147 -related ROS, controlled by the phospholipid flippase kinase Fpk1 and sphingolipids, and by mitochond

148 iated in large part through the phospholipid flippase kinases Fpk1 and Fpk2, whereas the slow signali

149 membrane, under control of the phospholipid flippases Lem3-Dnf1 and Lem3-Dnf2.

150 ATP8A2 is a P(4)-ATPase ("flippase") located in membranes of retinal photoreceptor

151 The class 4 P-type ATPases ("flippases") maintain membrane asymmetry by translocating

152 the detergent-solubilized and purified yeast flippase may result in more than 1 order of magnitude in

153 e acid transport, including the phospholipid flippase MDR2.

154 g transporter (MDR1) and phosphatidylcholine flippase (MDR2).

155 and that the transport is probably protein (flippase)-mediated.

156 se was followed by a slower phase reflecting flippase-mediated translocation of phospholipids from th

157 chanisms that could modulate the function of flippase might be important in phospholipid asymmetry di

158 Results with a small molecule phospholipid flippase mimetic suggest azPC acts intracellularly and t

159 ch were suppressed by overexpressing the LPS flippase MsbA (BCAL2408), suggesting that lipid A molecu

160 We studied the bacterial lipid flippase MsbA by luminescence resonance energy transfer

161 e have determined the structure of the lipid flippase MsbA from Escherichia coli by x-ray crystallogr

162 e have determined the structure of the lipid flippase MsbA from Vibrio cholera (VC-MsbA) to 3.8A.

163 sed on three crystal structures of the lipid flippase MsbA, envisions a large-amplitude motion that d

164 ble substrate for the Escherichia coli lipid flippase MsbA.

165 nct from that observed for the E. coli lipid flippase MsbA.

166 x-ray structures of the bacterial ABC lipid flippase, MsbA, trapped in different conformations, two

167 We also used a combination of flippase mutants that either gain or lose the ability to

168 The protein appears to function as a flippase of all-trans-retinaldehyde and/or its derivativ

169 at opsin is the ATP-independent phospholipid flippase of photoreceptor discs.

170 genesis and homologous to known and putative flippases of the MOP (multidrug/oligo-saccharidyl-lipid/

171 y; (c) the eukaryotic oligosaccharidyl-lipid flippase (OLF) family and (d) the bacterial mouse virule

172 was recently shown to be an ATP-independent flippase (or scramblase) that equilibrates phospholipids

173 unctionally critical sulfhydryl group in the flippase protein is buried in a hydrophobic environment

174 strate that the ER has at least two distinct flippase proteins, each specifically capable of transloc

175 e ABC1 may act as a phospholipid/cholesterol flippase, providing lipid to bound apoA-I, or to the out

176 R-Cas9-mediated genome editing to generate a flippase recognition target (FRT)-dependent conditional

177 Homologous recombination was used to insert flippase recognition target recombination sites around e

178 ble isoprenyl monophosphates showed that MPD flippase recognizes the dolichol chain of MPD, preferrin

179 pecific transport proteins; (iii) functional flippases represent approximately 1% (w/w) of ER membran

180 hree phospholipids is likely due to the same flippase(s) rather than distinct, phospholipid-specific

181 This aminophospholipid "flippase" selectively transports PS to the cytosolic lea

182 cted to be facilitated by membrane proteins (flippases) since transport across protein-free membranes

183 s and is the first example of a phospholipid flippase that belongs to the major facilitator superfami

184 holipid ATPase10 (ALA10) is a P4-type ATPase flippase that internalizes exogenous phospholipids acros

185 e AMINOPHOSPHOLIPID ATPASE 3 (ALA3), a lipid flippase that plays a critical role in vesicle formation

186 sis are known, the identity of the essential flippase that translocates it across the cytoplasmic mem

187 rom the oligosaccharide-diphosphate dolichol flippase that translocates Man(5)GlcNAc(2)-PP-dolichol,

188 s of peptidoglycan; what was missing was the flippase that translocates the lipid-anchored precursors

189 ymmetry occurs despite the presence of other flippases that flip PS and/or PE.

190 Flippases that operate at the plasma membrane of eukaryo

191 TPases are a family of putative phospholipid flippases that regulate lipid membrane asymmetry, which

192 itated by well characterized ER phospholipid flippases that remain to be identified at the molecular

193 Fpk1 phosphorylates and stimulates flippases that translocate aminoglycerophospholipids fro

194 he other hand, ATP-independent bidirectional flippases that translocate lipids in biogenic compartmen

195 haride) exporter superfamily, which includes flippases that translocate undecaprenyl diphosphate-link

196 es, has been devised to identify protein(s) (flippases) that could mediate the thermodynamically unfa

197 ) are putative phospholipid translocases, or flippases, that translocate specific phospholipid substr

198 adhesion kinase, the H(+)/K(+) ATPase beta (flippase), the hematopoietic cell multidrug resistance p

199 250-nm diameter vesicles containing a single flippase, the half-time was 3.3 min.

200 al membrane proteins called translocases or "flippases." The bacterial genes proposed to encode these

201 ranslocation of lipid II must be assisted by flippases thought to shield the disaccharide-pentapeptid

202 roteins that function as lipid transporters (flippases) to accelerate flipping to a physiologically r

203 P4 ATPase flippases translocate primarily phosphatidylserine and,

204 P4-ATPases (flippases) translocate specific phospholipids such as ph

205 ility that antagonists of the canonical MurJ flippase trigger expression of an alternate translocase

206 preparations with a higher average number of flippases/vesicle.

207 e promise for future attempts to isolate the flippase via an affinity approach.

208 idence supporting the existence of dedicated flippases was recently obtained through biochemical reco

209 g a framework to guide the purification of a flippase, we now describe an assay to measure the transb

210 o Escherichia coli mviN, a putative lipid II flippase, which F. tularensis uses to evade activation o

211 porters is the erythrocyte aminophospholipid flippase, which selectively transports phosphatidylserin

212 opping of the carrier lipid is mediated by a flippase, which would provide a mechanism for the recycl

213 These proteins are likely to be the flippases, which are required to translocate natural pho

214 ALA1 and ALA2 are flippases, which are transmembrane lipid transporter pro