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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

Comparison of averaged z-positions of the Cα atom (black) and the side chain centroid (red) of each amino acid residue at the POPC (left) and POPG (right) membrane surface. The green and blue dashed lines correspond, respectively, to the average z-position of phosphorus atoms (z = 0) and carbon atoms of the lipid ester groups.
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fig6: Comparison of averaged z-positions of the Cα atom (black) and the side chain centroid (red) of each amino acid residue at the POPC (left) and POPG (right) membrane surface. The green and blue dashed lines correspond, respectively, to the average z-position of phosphorus atoms (z = 0) and carbon atoms of the lipid ester groups.

Mentions: In order to compare the binding orientations of hIAPP at POPC bilayer with those at POPG bilayers, we plot in Figure 6 the z-position of each amino acid residue of hIAPP relative to the average z-position (z = 0) of phosphorus atoms, averaged over the last 20 ns of twelve independent 120 ns MD runs. It is seen that, at the POPC membrane surface, the z-position of each residues is very close to the position of lipid phosphorus atoms (green dotted line). The similar z-position of all residues reflects the uncertainty of peptide orientations. At the POPG bilayer surface, the positively charged residues K1 and R11 anchor to the bilayer surface by electrostatic interactions, and the z-position gradually increases from the N-terminal to C-terminal residues. The z-position of residues in Figure 6 shows that the α-helix region (residues 5~19) of hIAPP is parallel to the POPG bilayer surface, with residues R11, F15, and S19 pointing to the lipid bilayer while the hydrophobic residues L12, A13, L16, and V17 exposed to the water, revealing a preferred binding orientation at anionic POPG bilayers.


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

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

Comparison of averaged z-positions of the Cα atom (black) and the side chain centroid (red) of each amino acid residue at the POPC (left) and POPG (right) membrane surface. The green and blue dashed lines correspond, respectively, to the average z-position of phosphorus atoms (z = 0) and carbon atoms of the lipid ester groups.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig6: Comparison of averaged z-positions of the Cα atom (black) and the side chain centroid (red) of each amino acid residue at the POPC (left) and POPG (right) membrane surface. The green and blue dashed lines correspond, respectively, to the average z-position of phosphorus atoms (z = 0) and carbon atoms of the lipid ester groups.
Mentions: In order to compare the binding orientations of hIAPP at POPC bilayer with those at POPG bilayers, we plot in Figure 6 the z-position of each amino acid residue of hIAPP relative to the average z-position (z = 0) of phosphorus atoms, averaged over the last 20 ns of twelve independent 120 ns MD runs. It is seen that, at the POPC membrane surface, the z-position of each residues is very close to the position of lipid phosphorus atoms (green dotted line). The similar z-position of all residues reflects the uncertainty of peptide orientations. At the POPG bilayer surface, the positively charged residues K1 and R11 anchor to the bilayer surface by electrostatic interactions, and the z-position gradually increases from the N-terminal to C-terminal residues. The z-position of residues in Figure 6 shows that the α-helix region (residues 5~19) of hIAPP is parallel to the POPG bilayer surface, with residues R11, F15, and S19 pointing to the lipid bilayer while the hydrophobic residues L12, A13, L16, and V17 exposed to the water, revealing a preferred binding orientation at anionic POPG bilayers.

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