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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

(a) Molecular structures of a POPC/POPG lipid molecule. Different lipid groups are colored differently: choline/glycerol in black, phosphate group in red, ester group in green, and other carbon atoms in blue. (b) Electron density profiles of the lipid choline/glycerol, phosphate, and ester groups. Here, we set the z-position of bilayer at zero (z = 0). (c) Number of H-bonds formed between each amino residue of hIAPP and the three different groups in lipid heads: choline (POPC)/glycerol (POPG), phosphate, and ester groups.
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fig7: (a) Molecular structures of a POPC/POPG lipid molecule. Different lipid groups are colored differently: choline/glycerol in black, phosphate group in red, ester group in green, and other carbon atoms in blue. (b) Electron density profiles of the lipid choline/glycerol, phosphate, and ester groups. Here, we set the z-position of bilayer at zero (z = 0). (c) Number of H-bonds formed between each amino residue of hIAPP and the three different groups in lipid heads: choline (POPC)/glycerol (POPG), phosphate, and ester groups.

Mentions: Through detailed structural analysis, we find that although the chemical components of POPC and POPG lipids are similar, the locations of these components in the membrane are different. We plot in Figure 7 the electron density of POPC and POPG along the membrane normal (i.e., z-axis), as done in a previous study of lipid bilayers [82]. It shows that the POPC ester, phosphate, and choline groups are located in turn from the membrane center (z = 0) to the water solution, while the POPG phosphate and glycerol groups are nearly at the same depth in the membrane with ester groups buried deeper. In addition, the peak value of each POPC headgroup component is smaller than that of POPG, and the average area per lipid of POPC membrane is higher than that of POPG (61.6 ± 0.7 Å2 versus 54.6 ± 0.6 Å2), consistent with previous computational and experimental studies [82, 93, 94]. Overall, the headgroup region of the POPC bilayer is less compact than that of the POPG bilayer, which is helpful for the insertion of hIAPP monomer into POPC membrane. The symmetric distributions of POPC/POPG lipid atoms in the upper and lower leaflets of the bilayer reveal that hIAPP monomer does not cause membrane disruption, in agreement with experimental observations [29, 95].


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

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

(a) Molecular structures of a POPC/POPG lipid molecule. Different lipid groups are colored differently: choline/glycerol in black, phosphate group in red, ester group in green, and other carbon atoms in blue. (b) Electron density profiles of the lipid choline/glycerol, phosphate, and ester groups. Here, we set the z-position of bilayer at zero (z = 0). (c) Number of H-bonds formed between each amino residue of hIAPP and the three different groups in lipid heads: choline (POPC)/glycerol (POPG), phosphate, and ester groups.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4663351&req=5

fig7: (a) Molecular structures of a POPC/POPG lipid molecule. Different lipid groups are colored differently: choline/glycerol in black, phosphate group in red, ester group in green, and other carbon atoms in blue. (b) Electron density profiles of the lipid choline/glycerol, phosphate, and ester groups. Here, we set the z-position of bilayer at zero (z = 0). (c) Number of H-bonds formed between each amino residue of hIAPP and the three different groups in lipid heads: choline (POPC)/glycerol (POPG), phosphate, and ester groups.
Mentions: Through detailed structural analysis, we find that although the chemical components of POPC and POPG lipids are similar, the locations of these components in the membrane are different. We plot in Figure 7 the electron density of POPC and POPG along the membrane normal (i.e., z-axis), as done in a previous study of lipid bilayers [82]. It shows that the POPC ester, phosphate, and choline groups are located in turn from the membrane center (z = 0) to the water solution, while the POPG phosphate and glycerol groups are nearly at the same depth in the membrane with ester groups buried deeper. In addition, the peak value of each POPC headgroup component is smaller than that of POPG, and the average area per lipid of POPC membrane is higher than that of POPG (61.6 ± 0.7 Å2 versus 54.6 ± 0.6 Å2), consistent with previous computational and experimental studies [82, 93, 94]. Overall, the headgroup region of the POPC bilayer is less compact than that of the POPG bilayer, which is helpful for the insertion of hIAPP monomer into POPC membrane. The symmetric distributions of POPC/POPG lipid atoms in the upper and lower leaflets of the bilayer reveal that hIAPP monomer does not cause membrane disruption, in agreement with experimental observations [29, 95].

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