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Binding Orientations and Lipid Interactions of Human Amylin at Zwitterionic and Anionic Lipid Bilayers.

Qian Z, Jia Y, Wei G - J Diabetes Res (2015)

Bottom Line: The results are compared with those of hIAPP at anionic palmitoyloleoyl-phosphatidylglycerol (POPG) bilayers.Peptide-lipid interaction analyses show that the different binding features of hIAPP at POPC and POPG bilayers are attributed to different magnitudes of electrostatic and hydrogen-bonding interactions with lipids.This study provides mechanistic insights into the different interaction behaviors of hIAPP with zwitterionic and anionic lipid bilayers.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Surface Physics, Key Laboratory for Computational Physical Sciences (Ministry of Education), and Department of Physics, Fudan University, Shanghai 200433, China.

ABSTRACT
Increasing evidence suggests that the interaction of human islet amyloid polypeptide (hIAPP) with lipids may facilitate hIAPP aggregation and cause the death of pancreatic islet β-cells. However, the detailed hIAPP-membrane interactions and the influences of lipid compositions are unclear. In this study, as a first step to understand the mechanism of membrane-mediated hIAPP aggregation, we investigate the binding behaviors of hIAPP monomer at zwitterionic palmitoyloleoyl-phosphatidylcholine (POPC) bilayer by performing atomistic molecular dynamics simulations. The results are compared with those of hIAPP at anionic palmitoyloleoyl-phosphatidylglycerol (POPG) bilayers. We find that the adsorption of hIAPP to POPC bilayer is mainly initiated from the C-terminal region and the peptide adopts a helical structure with multiple binding orientations, while the adsorption to POPG bilayer is mostly initiated from the N-terminal region and hIAPP displays one preferential binding orientation, with its hydrophobic residues exposed to water. hIAPP monomer inserts into POPC lipid bilayers more readily than into POPG bilayers. Peptide-lipid interaction analyses show that the different binding features of hIAPP at POPC and POPG bilayers are attributed to different magnitudes of electrostatic and hydrogen-bonding interactions with lipids. This study provides mechanistic insights into the different interaction behaviors of hIAPP with zwitterionic and anionic lipid bilayers.

No MeSH data available.


Related in: MedlinePlus

Four different initial states of simulated hIAPP-POPC systems. The side chain of residue K1 in S(0) points toward the POPC membrane surface. The other orientations of hIAPP are generated by rotating the hIAPP helix in (a) by 90°, 180°, and 270° around the helix axis. The other three different initial states are labeled as S(90), S(180), and S(270), according to the rotation angle. The peptide is shown in cartoon representation, with the helix (residues 5–28) in purple, the coil in orange and the other secondary structure in cyan. Bond representation is given for each amino acid residue, except for K1 in van der Waals (vdW) representation. The lipids are shown in grey line representation and phosphorus atoms as tan spheres. For clarity, counterions and water molecules are not shown.
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Related In: Results  -  Collection


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fig1: Four different initial states of simulated hIAPP-POPC systems. The side chain of residue K1 in S(0) points toward the POPC membrane surface. The other orientations of hIAPP are generated by rotating the hIAPP helix in (a) by 90°, 180°, and 270° around the helix axis. The other three different initial states are labeled as S(90), S(180), and S(270), according to the rotation angle. The peptide is shown in cartoon representation, with the helix (residues 5–28) in purple, the coil in orange and the other secondary structure in cyan. Bond representation is given for each amino acid residue, except for K1 in van der Waals (vdW) representation. The lipids are shown in grey line representation and phosphorus atoms as tan spheres. For clarity, counterions and water molecules are not shown.

Mentions: The helical region of hIAPP monomer was initially orientated parallel to the membrane surface with a minimum distance ≥1.4 nm between the peptide and the POPC bilayer. We chose four different starting orientations of hIAPP with respect to POPC bilayer surface (see Figure 1) so that the peptide was allowed to adjust itself before adsorption to the bilayer surface. In the initial state of S(0), the side chain of residue K1 points toward the membrane surface. The initial state S(90), S(180), and S(270) were generated by rotating the hIAPP peptide in S(0) by 90°, 180°, and 270° around the axis of the helix, respectively. Each hIAPP-membrane system was immersed in a SPC water [65] box.


Binding Orientations and Lipid Interactions of Human Amylin at Zwitterionic and Anionic Lipid Bilayers.

Qian Z, Jia Y, Wei G - J Diabetes Res (2015)

Four different initial states of simulated hIAPP-POPC systems. The side chain of residue K1 in S(0) points toward the POPC membrane surface. The other orientations of hIAPP are generated by rotating the hIAPP helix in (a) by 90°, 180°, and 270° around the helix axis. The other three different initial states are labeled as S(90), S(180), and S(270), according to the rotation angle. The peptide is shown in cartoon representation, with the helix (residues 5–28) in purple, the coil in orange and the other secondary structure in cyan. Bond representation is given for each amino acid residue, except for K1 in van der Waals (vdW) representation. The lipids are shown in grey line representation and phosphorus atoms as tan spheres. For clarity, counterions and water molecules are not shown.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4663351&req=5

fig1: Four different initial states of simulated hIAPP-POPC systems. The side chain of residue K1 in S(0) points toward the POPC membrane surface. The other orientations of hIAPP are generated by rotating the hIAPP helix in (a) by 90°, 180°, and 270° around the helix axis. The other three different initial states are labeled as S(90), S(180), and S(270), according to the rotation angle. The peptide is shown in cartoon representation, with the helix (residues 5–28) in purple, the coil in orange and the other secondary structure in cyan. Bond representation is given for each amino acid residue, except for K1 in van der Waals (vdW) representation. The lipids are shown in grey line representation and phosphorus atoms as tan spheres. For clarity, counterions and water molecules are not shown.
Mentions: The helical region of hIAPP monomer was initially orientated parallel to the membrane surface with a minimum distance ≥1.4 nm between the peptide and the POPC bilayer. We chose four different starting orientations of hIAPP with respect to POPC bilayer surface (see Figure 1) so that the peptide was allowed to adjust itself before adsorption to the bilayer surface. In the initial state of S(0), the side chain of residue K1 points toward the membrane surface. The initial state S(90), S(180), and S(270) were generated by rotating the hIAPP peptide in S(0) by 90°, 180°, and 270° around the axis of the helix, respectively. Each hIAPP-membrane system was immersed in a SPC water [65] box.

Bottom Line: The results are compared with those of hIAPP at anionic palmitoyloleoyl-phosphatidylglycerol (POPG) bilayers.Peptide-lipid interaction analyses show that the different binding features of hIAPP at POPC and POPG bilayers are attributed to different magnitudes of electrostatic and hydrogen-bonding interactions with lipids.This study provides mechanistic insights into the different interaction behaviors of hIAPP with zwitterionic and anionic lipid bilayers.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Surface Physics, Key Laboratory for Computational Physical Sciences (Ministry of Education), and Department of Physics, Fudan University, Shanghai 200433, China.

ABSTRACT
Increasing evidence suggests that the interaction of human islet amyloid polypeptide (hIAPP) with lipids may facilitate hIAPP aggregation and cause the death of pancreatic islet β-cells. However, the detailed hIAPP-membrane interactions and the influences of lipid compositions are unclear. In this study, as a first step to understand the mechanism of membrane-mediated hIAPP aggregation, we investigate the binding behaviors of hIAPP monomer at zwitterionic palmitoyloleoyl-phosphatidylcholine (POPC) bilayer by performing atomistic molecular dynamics simulations. The results are compared with those of hIAPP at anionic palmitoyloleoyl-phosphatidylglycerol (POPG) bilayers. We find that the adsorption of hIAPP to POPC bilayer is mainly initiated from the C-terminal region and the peptide adopts a helical structure with multiple binding orientations, while the adsorption to POPG bilayer is mostly initiated from the N-terminal region and hIAPP displays one preferential binding orientation, with its hydrophobic residues exposed to water. hIAPP monomer inserts into POPC lipid bilayers more readily than into POPG bilayers. Peptide-lipid interaction analyses show that the different binding features of hIAPP at POPC and POPG bilayers are attributed to different magnitudes of electrostatic and hydrogen-bonding interactions with lipids. This study provides mechanistic insights into the different interaction behaviors of hIAPP with zwitterionic and anionic lipid bilayers.

No MeSH data available.


Related in: MedlinePlus