Evaluation of lipid‐binding properties of the N‐terminal helical segments in human apolipoprotein A‐I using fragment peptides

Tanaka, Masafumi; Tanaka, Toshitaka; Ohta, Shinya; Kawakami, Toru; Konno, Hiroyuki; Akaji, Kenichi; Aimoto, Saburo; Saito, Hiroyuki

doi:10.1002/psc.1092

Cited by 14 publications

(14 citation statements)

References 43 publications

(50 reference statements)

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“…Taking into account the fact that the 1-43 peptide has a greater ability to bind to lipids than the 44-65 peptide [29], it is plausible that hydrophobic interactions play a role not only in lipid binding but also in fibril formation of the apoA-I peptides. To support this idea, substitution of Tyr-18 located at the center of the most hydrophobic region in residues 1-43 with a proline residue caused not only impaired lipid binding [29] but also strong inhibition of fibril formation of the 1-43 peptide ( Supplementary Fig. S5).…”

Section: Discussionmentioning

confidence: 99%

The extreme N‐terminal region of human apolipoprotein A‐I has a strong propensity to form amyloid fibrils

et al. 2013

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a b s t r a c tThe N-terminal 1-83 residues of apolipoprotein A-I (apoA-I) have a strong propensity to form amyloid fibrils, in which the 46-59 segment was reported to aggregate to form amyloid-like fibrils. In this study, we demonstrated that a fragment peptide comprising the extreme N-terminal 1-43 residues strongly forms amyloid fibrils with a transition to b-sheet-rich structure, and that the G26R point mutation enhances the fibril formation of this segment. Our results suggest that in addition to the 46-59 segment, the extreme N-terminal region plays a crucial role in the development of amyloid fibrils by the N-terminal fragment of amyloidogenic apoA-I variants. Structured summary of protein interactions:apoA-I and apoA-I bind by fluorescence technology (1, 2, 3) apoA-I and apoA-I bind by atomic force microscopy (View interaction) apoA-I and apoA-I bind by dynamic light scattering (1, 2)

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Section: Discussionmentioning

confidence: 99%

The extreme N‐terminal region of human apolipoprotein A‐I has a strong propensity to form amyloid fibrils

et al. 2013

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“…Peptides-To further evaluate the effects of the G26R mutation on the lipid-binding and fibril forming properties of the N-terminal residues of apoA-I, we used the apoA-I 8 -33 fragment because this peptide contains a high lipid affinity region that forms ␣-helical structure upon lipid binding (49) as well as a strong fibril-forming region (20). The helical wheel diagram in Fig.…”

Section: Membrane-binding and Fibril-forming Properties Of Apoa-i 8 -mentioning

confidence: 99%

Amyloidogenic Mutation Promotes Fibril Formation of the N-terminal Apolipoprotein A-I on Lipid Membranes

Mizuguchi

Ogata

Mikawa

et al. 2015

Journal of Biological Chemistry

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Background:The N-terminal fragment of amyloidogenic apoA-I mutants deposits as fibrils by unknown mechanisms. Results: The G26R mutation partially prevents helix formation of the N-terminal fragment upon lipid binding, thereby facilitating ␤-transition and fibril formation. Conclusion: Membrane binding modulates fibril formation of apoA-I through partially destabilized helical conformation. Significance: The results reveal a new pathway for amyloid fibril formation by apoA-I.

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“…13) Primary sequences of the synthetic peptides used in the present study are listed in Table 1. The N-and the C-termini were capped with an acetyl group and an amide group, respectively.…”

Section: Methodsmentioning

confidence: 99%

Deletion of Single Amino Acid E235 Affects the Structure and Lipid Interaction of Human Apolipoprotein A-I C-Terminal Peptides

Tanaka

Sugiura

et al. 2009

CHEMICAL & PHARMACEUTICAL BULLETIN

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Human apolipoprotein (apo) A-I, a 243 amino acid protein, is the major protein component of high-density lipoprotein (HDL). ApoA-I plays an important role in lipoprotein metabolism, reverse cholesterol transport pathway, and protection against the development of atherosclerosis.1) In reverse cholesterol transport pathway, lipid-free or lipid-poor apoA-I molecules remove cholesterol from peripheral cells and transport it in the form of HDL back to the liver for excretion.2) Lipid-free apoA-I is folded into two domains, comprising an N-terminal domain forming a four-helix bundle and a discrete C-terminal domain, which is predominantly involved in lipid-protein interactions. These interactions are critical for HDL generation, including initial lipid binding and cholesterol efflux from plasma membrane.3) ApoA-I Nichinan, a naturally occurring human apoA-I variant with a deletion of E235 located in the C-terminus, is associated with low HDL cholesterolemia probably due to the impaired lipid binding and cellular interactions. 4,5) Computational analysis of the amino acid sequence of human apoA-I reveals that residues 44-243, encoded by exon 4, is composed of 11-or 22-amino acid tandem repeats, which can form amphipathic a-helices mostly punctuated by proline residues. 6) Studies of synthetic peptides corresponding to each of 22-residue amphipathic segments of apoA-I have shown that the last repeated helix (residues 220-241) has greatest lipid affinity. 7,8) In addition, our previous studies using deletion mutants of apoA-I demonstrated that deletion in the last helix leads to significant decreases in lipid-binding affinity compared to intact apoA-I. 9,10) A lack of E235 in apoA-I Nichinan variant is considered to bring about at least two possible structural influences such as 1) a negative charge ablation and 2) disturbance of amino acid distribution on the helix cross-section (i.e., loss of amphipathicity) (Fig. 1). Previously, Panagotopulos et al. have revealed that the E235K mutation in full-length apoA-I does not affect lipid microsolubilization and cellular cholesterol efflux, 11) suggesting the possibility that amphipathic nature of the C-terminal region in apoA-I Nichinan is influenced by the disturbance of amino acid distribution caused by E235 deletion. To examine the influences of E235 deletion on the a-helical structure and lipid interaction of the C-terminal region in apoA-I, we used a series of variant peptides corresponding to residues 220-241 of the apoA-I molecule in addition of DE235: E235A in which E235 was substituted with nonpolar alanine residue to examine the influence of a negative charge ablation, and L230P in which L230 was substituted with proline residue to disrupt the putative a-helical structure. We previously demonstrated that proline insertion instead of leucine residue at position 230 disrupts the C-ter- The C-terminal domain of apolipoprotein (apo) A-I plays an important role in lipid binding. ApoA-I Nichinan, a naturally occurring human apoA-I variant with a deletion of E235 located i...

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Evaluation of lipid‐binding properties of the N‐terminal helical segments in human apolipoprotein A‐I using fragment peptides

Cited by 14 publications

References 43 publications

The extreme N‐terminal region of human apolipoprotein A‐I has a strong propensity to form amyloid fibrils

The extreme N‐terminal region of human apolipoprotein A‐I has a strong propensity to form amyloid fibrils

Amyloidogenic Mutation Promotes Fibril Formation of the N-terminal Apolipoprotein A-I on Lipid Membranes

Deletion of Single Amino Acid E235 Affects the Structure and Lipid Interaction of Human Apolipoprotein A-I C-Terminal Peptides

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