Helix-helix interactions in reconstituted high-density lipoproteins

Lins, Laurence; Brasseur, Robert; Pauw, Michel De; Biervliet, J.P. Van; Ruysschaert, Jean Marie; Rosseneu, Maryvonne; Vanloo, Berlinda

doi:10.1016/0005-2760(95)00080-v

Cited by 30 publications

(29 citation statements)

References 16 publications

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“…Modeling studies have suggested that the mode of assembly of adjacent amphipathic helical repeats around the edge of a discoidal complex is determined by both the hydrophobic character of the residues and by the charge complementary along the edge of the helices (46). From crystallography studies, helix-helix interactions inside lipid bilayers have been shown to include interhelical salt bridges, hydrogen bonds, or precise packing interactions (47).…”

Section: Table II Reaction Kinetics Of Recombinant Hdl Particles Withmentioning

confidence: 99%

Alteration in Apolipoprotein A-I 22-Mer Repeat Order Results in a Decrease in Lecithin:Cholesterol Acyltransferase Reactivity

Sorci‐Thomas

Curtiss

Parks

et al. 1997

Journal of Biological Chemistry

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Apolipoprotein A-I contains eight 22-amino acid and two 11-amino acid tandem repeats that comprise 80% of the mature protein. These repeating units are believed to be the basic motif responsible for lipid binding and lecithin:cholesterol acyltransferase (LCAT) activation. Computer analysis indicates that despite a fairly high degree of compositional similarity among the tandem repeats, significant differences in hydrophobic and amphipathic character exist. Our previous studies demonstrated that deletion of repeat 6 (143-164) or repeat 7 (165-186) resulted in a 98 -99% reduction of LCAT activation as compared with wild-type apoA-I. To determine the effects of substituting one of these repeats with a more hydrophobic repeat we constructed a mutant apoA-I protein in which residues 143-164 (repeat 6) were replaced with repeat 10 (residues 220 -241). The cloned mutant protein, 10F6 apoA-I, was expressed and purified from an Sf-9 cell baculoviral system and then analyzed using a number of biophysical and biochemical techniques. Recombinant complexes prepared at a 100: 5:1 molar ratio of L-␣-dimyristoylphosphatidylcholine: cholesterol:wild-type or 10F6 apoA-I showed a doublet corresponding to Stokes diameters of 114 and 108 Å on nondenaturing 4 -30% polyacrylamide gel electrophoresis. L-␣-Dimyristoylphosphatidylcholine 10F6 apoA-I complexes had a 5-6-fold lower apparent V max /apparent K m as compared with wild-type apoA-I containing particles. As expected, monoclonal antibody epitope mapping of the lipid-free and lipid-bound 10F6 apoA-I confirmed that a domain expressed between residues 143 and 165 normally found in wild-type apoA-I was absent. The region between residues 119 and 144 in 10F6 apoA-I showed a marked reduction in monoclonal antibody binding capacity. Therefore, we speculate that the 5-6-fold lower LCAT reactivity in 10F6 compared with wildtype apoA-I recombinant particles results from increased stabilization within the 121-165 amino acid domain due to more stable apoprotein helix phospholipid interactions as well as from conformational alterations among adjacent amphipathic helix repeats.

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Section: Table II Reaction Kinetics Of Recombinant Hdl Particles Withmentioning

confidence: 99%

Alteration in Apolipoprotein A-I 22-Mer Repeat Order Results in a Decrease in Lecithin:Cholesterol Acyltransferase Reactivity

Sorci‐Thomas

Curtiss

Parks

et al. 1997

Journal of Biological Chemistry

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“…As salt-bridge formation enhances the stability of apolipoproteins (23), it follows that the apoA-I in (A-I/A-II)rHDL should be resistant to unfolding compared with the apoA-I in (A-I)rHDL. To determine whether this was the case, the (A-I/A-II)rHDL and (A-I)rHDL were incubated for 0 -24 h with Gdn-HCl at pH 8.0 and the kinetics of the unfolding of apoA-I was assessed.…”

Section: Table I Composition Of (A-i)rhdl and (A-i/a-ii)rhdl After Inmentioning

confidence: 99%

Apolipoprotein A-II Inhibits High Density Lipoprotein Remodeling and Lipid-poor Apolipoprotein A-I Formation

Rye

Wee

Curtiss

et al. 2003

Journal of Biological Chemistry

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“…The blocked pentapeptides have 5 peptide bonds, each of which is allowed to have any of 6 different sets of dihedral angles, resulting in 6 5 or 7776 different structures. This stereoalphabet method was used previously to study the loop conformation for helix-helix interactions (21). The energy of peptide conformations are calculated by an all atom description of structures and the addition of van der Waals, electrostatic, internal and external hydrophobicity energy terms.…”

Section: Modeling Structure Propertiesmentioning

confidence: 99%

“…The energy of peptide conformations are calculated by an all atom description of structures and the addition of van der Waals, electrostatic, internal and external hydrophobicity energy terms. The van der Waals contribution was calculated using the 6-12 Lennard-Jones description of the energy of interactions between unbonded atoms (21). The Coulomb's equation was used for electrostatic interactions between unbonded charged atoms with a dielectric 'constant' sigmoidally varying from 1 to 80 with distance between atoms and, using FCPAC partial atomic charges (22).…”

Section: Modeling Structure Propertiesmentioning

confidence: 99%

Juxtamembrane Protein Segments that Contribute to Recruitment of Cholesterol into Domains

et al. 2006

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We investigated the properties of several peptides with sequences related to LWYIK, a segment found in the gp41 protein of HIV and believed to play a role in sequestering this protein to a cholesterol-rich domain in the membrane. This segment fulfills the requirements to be classified as a CRAC motif that has been suggested to predict those proteins that will partition into cholesterolrich regions of the membrane. All of the peptides were studied with the terminal amino and carboxyl groups blocked, i.e. as N-acetyl-peptide-amides. Effects of cholesterol on the intensity of W emission generally parallel DSC evidence of sequestration of cholesterol. Modeling studies indicate that all of these peptides tend to partition with their mass center at the membrane interface at the level of the hydroxyl of cholesterol. Interaction with cholesterol is dual: van der Waals interactions between mainly hydrophobic surfaces and, electrostatic stabilization of the cholesterol OH group. Thus, both experiments and modeling studies indicate that preference of CRAC motifs for cholesterol-rich domains might be related to a membrane interfacial preference of the motif, to a capacity to wrap and block the cholesterol polar OH by H-bond interactions and to a capacity for peptide aromatic side chains to stack with cholesterol. These results were supported by studies of single mutations in the gp41 protein of HIV-1, in which L 679 is replaced with I. Despite the similarity of the properties of these amino acid residues, this single substitution resulted in a marked decrease in the capability of JC53-BL HeLa-based HIV-1 indicator cells to form syncytia.It has been demonstrated that peptides and proteins can cause the redistribution of cholesterol in membranes (1). Triggering domain formation may play an important role in signal transduction (2). One class of domains thought to be present in biological membranes has been termed "rafts". Although there is controversy about the nature and prevalence of such domains, it is well established that caveolae are distinct domains in the membrane with many chemical and physical properties similar to those proposed for "rafts".

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Helix-helix interactions in reconstituted high-density lipoproteins

Cited by 30 publications

References 16 publications

Alteration in Apolipoprotein A-I 22-Mer Repeat Order Results in a Decrease in Lecithin:Cholesterol Acyltransferase Reactivity

Alteration in Apolipoprotein A-I 22-Mer Repeat Order Results in a Decrease in Lecithin:Cholesterol Acyltransferase Reactivity

Apolipoprotein A-II Inhibits High Density Lipoprotein Remodeling and Lipid-poor Apolipoprotein A-I Formation

Juxtamembrane Protein Segments that Contribute to Recruitment of Cholesterol into Domains

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