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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

Index of residues closest to the POPC membrane surface as a function of time. A residue is considered to be the one closest to the bilayer surface if the z-position of its centroid is the smallest relative to the average z-position of the phosphorus atoms. In water solution, the closest residue index varies with time; once the peptide adsorbs to the membrane surface, the index of the residue closest to the POPC bilayer rarely changes.
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fig2: Index of residues closest to the POPC membrane surface as a function of time. A residue is considered to be the one closest to the bilayer surface if the z-position of its centroid is the smallest relative to the average z-position of the phosphorus atoms. In water solution, the closest residue index varies with time; once the peptide adsorbs to the membrane surface, the index of the residue closest to the POPC bilayer rarely changes.

Mentions: We have calculated the z-position of the centroid of each residue with respect to the POPC bilayer surface and present the closest residue index as a function of time in Figure 2. We observe that in 11 out of 12 MD runs, the C-terminal residues are observed to adsorb to the POPC bilayer surface prior to the N-terminal residues, namely, the adsorption of hIAPP monomer is initiated from the C-terminal residues. This membrane adsorption behavior of hIAPP may be attributed to the dipole-dipole interaction between the polar residues (such as Ser34, Asn35, and Thr36) and the zwitterionic POPC lipids. In our previous study [56], we observed that the positively charged residues K1 and R11 in the N-terminal region have a preference to adsorb to the anionic POPG lipid bilayer. Previous experimental studies reported that the N-terminal residues are involved in the membrane entry of hIAPP peptide [32], and result in membrane damage at high peptide concentration [19, 89]. Our results show that the adsorption process of hIAPP monomer to POPC and POPG bilayer membranes is distinct, which may lead to different binding behaviors and may influence the aggregation of membrane-bound hIAPPs.


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

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

Index of residues closest to the POPC membrane surface as a function of time. A residue is considered to be the one closest to the bilayer surface if the z-position of its centroid is the smallest relative to the average z-position of the phosphorus atoms. In water solution, the closest residue index varies with time; once the peptide adsorbs to the membrane surface, the index of the residue closest to the POPC bilayer rarely changes.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig2: Index of residues closest to the POPC membrane surface as a function of time. A residue is considered to be the one closest to the bilayer surface if the z-position of its centroid is the smallest relative to the average z-position of the phosphorus atoms. In water solution, the closest residue index varies with time; once the peptide adsorbs to the membrane surface, the index of the residue closest to the POPC bilayer rarely changes.
Mentions: We have calculated the z-position of the centroid of each residue with respect to the POPC bilayer surface and present the closest residue index as a function of time in Figure 2. We observe that in 11 out of 12 MD runs, the C-terminal residues are observed to adsorb to the POPC bilayer surface prior to the N-terminal residues, namely, the adsorption of hIAPP monomer is initiated from the C-terminal residues. This membrane adsorption behavior of hIAPP may be attributed to the dipole-dipole interaction between the polar residues (such as Ser34, Asn35, and Thr36) and the zwitterionic POPC lipids. In our previous study [56], we observed that the positively charged residues K1 and R11 in the N-terminal region have a preference to adsorb to the anionic POPG lipid bilayer. Previous experimental studies reported that the N-terminal residues are involved in the membrane entry of hIAPP peptide [32], and result in membrane damage at high peptide concentration [19, 89]. Our results show that the adsorption process of hIAPP monomer to POPC and POPG bilayer membranes is distinct, which may lead to different binding behaviors and may influence the aggregation of membrane-bound hIAPPs.

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