Spontaneous reconstitution of discoidal HDL from sphingomyelin-containing model membranes by apolipoprotein A-I

Fukuda, Masahiro; Nakano, Minoru; Sriwongsitanont, Supaporn; Ueno, Masaki; Kuroda, Yoshihiro; Handa, Tetsurou

doi:10.1194/jlr.m600495-jlr200

Cited by 31 publications

(43 citation statements)

References 41 publications

(47 reference statements)

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“…5A). Consistent with the known membrane microsolubilizing activity of apoA-1 (26,27), a decrease in the light-scattering intensity was also observed for susceptible liposomes (Fig. 5A).…”

Section: Tlf Membrane Binding Is Facilitated By Low Ph and Mediated Bysupporting

confidence: 67%

“…We found that each of the protein components of TLF, Hpr, apoL-1, and indeed the HDL ubiquitous protein apoA-1 elicited the leakage of calcein from liposomes. The activity of apoA-1 was not unexpected as it is known to interact with cellular membranes with the concomitant formation of structures reminiscent of nascent HDL (26,27). Both of the unique protein components of TLF, apoL-1 and Hpr, efficiently permeabilized target liposomes.…”

Section: Discussionmentioning

confidence: 96%

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Membrane Permeabilization by Trypanosome Lytic Factor, a Cytolytic Human High Density Lipoprotein

Harrington

Howell

Hajduk

2009

Journal of Biological Chemistry

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Trypanosome lytic factor (TLF) is a subclass of human high density lipoprotein (HDL) that mediates an innate immune killing of certain mammalian trypanosomes, most notably Trypanosoma brucei brucei, the causative agent of a wasting disease in cattle. Mechanistically, killing is initiated in the lysosome of the target trypanosome where the acidic pH facilitates a membranedisrupting activity by TLF. Here we utilize a model liposome system to characterize the membrane binding and permeabilizing activity of TLF and its protein constituents, haptoglobinrelated protein (Hpr), apolipoprotein L-1 (apoL-1), and apolipoprotein A-1 (apoA-1). We show that TLF efficiently binds and permeabilizes unilamellar liposomes at lysosomal pH, whereas non-lytic human HDL exhibits inefficient permeabilizing activity. Purified, delipidated Hpr and apoL-1 both efficiently permeabilize lipid bilayers at low pH. Trypanosome lytic factor, apoL-1, and apoA-1 exhibit specificity for anionic membranes, whereas Hpr permeabilizes both anionic and zwitterionic membranes. Analysis of the relative particle sizes of susceptible liposomes reveals distinctly different membrane-active behavior for native TLF and the delipidated protein components. We propose that lysosomal membrane damage in TLF-susceptible trypanosomes is initiated by the stable association of the TLF particle with the lysosomal membrane and that this is a property unique to this subclass of human HDL.

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“…5A). Consistent with the known membrane microsolubilizing activity of apoA-1 (26,27), a decrease in the light-scattering intensity was also observed for susceptible liposomes (Fig. 5A).…”

Section: Tlf Membrane Binding Is Facilitated By Low Ph and Mediated Bysupporting

confidence: 67%

Section: Discussionmentioning

confidence: 96%

Membrane Permeabilization by Trypanosome Lytic Factor, a Cytolytic Human High Density Lipoprotein

Harrington

Howell

Hajduk

2009

Journal of Biological Chemistry

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“…An important question that has not been addressed is whether or not apo A-I can spontaneously solubilize more stable bilayers comprised of the phospholipids typically found in the plasma membrane of mammalian cells. In this case, no gel to liquid crystal phase transition to create lattice defects is apparent, although the presence of sphingomyelin, which creates a heterogeneous interface, can accelerate solubilization (56). The data in Fig.…”

Section: : Solubilization Of Exovesiculated Membrane Lipid Domains Bmentioning

confidence: 78%

Mechanism of ATP-binding Cassette Transporter A1-mediated Cellular Lipid Efflux to Apolipoprotein A-I and Formation of High Density Lipoprotein Particles

Vedhachalam

Duong

Nickel

et al. 2007

Journal of Biological Chemistry

305

310

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The ATP-binding cassette transporter A1 (ABCA1) plays a critical role in the biogenesis of high density lipoprotein (HDL) particles and in mediating cellular cholesterol efflux. The mechanism by which ABCA1 achieves these effects is not established, despite extensive investigation. Here, we present a model that explains the essential features, especially the effects of ABCA1 activity in inducing apolipoprotein (apo) A-I binding to cells and the compositions of the discoidal HDL particles that are produced. The apo A-I/ABCA1 reaction scheme involves three steps. First, there is binding of a small regulatory pool of apo A-I to ABCA1, thereby enhancing net phospholipid translocation to the plasma membrane exofacial leaflet; this leads to unequal lateral packing densities in the two leaflets of the phospholipid bilayer. Second, the resultant membrane strain is relieved by bending and by creation of exovesiculated lipid domains. The formation of highly curved membrane surface promotes high affinity binding of apo A-I to these domains. Third, this pool of bound apo A-I spontaneously solubilizes the exovesiculated domain to create discoidal nascent HDL particles. These particles contain two, three, or four molecules of apo A-I and a complement of membrane phospholipid classes together with some cholesterol. A key feature of this mechanism is that membrane bending induced by ABCA1 lipid translocase activity creates the conditions required for nascent HDL assembly by apo A-I. Overall, this mechanism is consistent with the known properties of ABCA1 and apo A-I and reconciles many of the apparently discrepant findings in the literature.

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“…The spontaneous solubilization is dependent on the cholesterol content and physical characteristics of the bilayer. 37 Typically, discoidal HDL particles contain two or three ApoA1 molecules. Larger particles include more protein.…”

Section: Apoa1 Structure and Function Hdl Particles And Apoa1mentioning

confidence: 99%

ApoA1 and ApoA1-specific self-antibodies in cardiovascular disease

Chistiakov

Orekhov

Bobryshev

2016

Laboratory Investigation

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Spontaneous reconstitution of discoidal HDL from sphingomyelin-containing model membranes by apolipoprotein A-I

Cited by 31 publications

References 41 publications

Membrane Permeabilization by Trypanosome Lytic Factor, a Cytolytic Human High Density Lipoprotein

Membrane Permeabilization by Trypanosome Lytic Factor, a Cytolytic Human High Density Lipoprotein

Mechanism of ATP-binding Cassette Transporter A1-mediated Cellular Lipid Efflux to Apolipoprotein A-I and Formation of High Density Lipoprotein Particles

ApoA1 and ApoA1-specific self-antibodies in cardiovascular disease

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