Limits...
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

hIAPP-POPC interaction energy (per lipid) for hIAPP with four different binding orientations. The interaction energy is decomposed into the vdW (black) and electrostatic (red) component, calculated using the final 20 ns data of each MD run.
© Copyright Policy - open-access
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4663351&req=5

fig5: hIAPP-POPC interaction energy (per lipid) for hIAPP with four different binding orientations. The interaction energy is decomposed into the vdW (black) and electrostatic (red) component, calculated using the final 20 ns data of each MD run.

Mentions: To identify the important interactions that stabilize each binding orientation of hIAPP at POPC bilayer, we plot in Figure 5 the interaction energy between a peptide and a lipid bilayer (per lipid). The interaction energy is decomposed into electrostatic and van der Waals (vdW) components. As seen from Figure 5 that hIAPPs with four binding orientations have nearly the same vdW interaction energy with lipids, and the electrostatic interaction energy is also similar. However, the electrostatic interaction is much stronger than vdW interaction, indicating that the former plays a dominant role in stabilizing the binding of hIAPP monomer to the POPC lipid bilayer although the net charge of a POPC lipid is zero. Different from our result, a recent MD study by Zhao et al. reported that the electrostatic and vdW interaction energy between hIAPP ion-channel and a DOPC bilayer are quite similar [37].


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

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

hIAPP-POPC interaction energy (per lipid) for hIAPP with four different binding orientations. The interaction energy is decomposed into the vdW (black) and electrostatic (red) component, calculated using the final 20 ns data of each MD run.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig5: hIAPP-POPC interaction energy (per lipid) for hIAPP with four different binding orientations. The interaction energy is decomposed into the vdW (black) and electrostatic (red) component, calculated using the final 20 ns data of each MD run.
Mentions: To identify the important interactions that stabilize each binding orientation of hIAPP at POPC bilayer, we plot in Figure 5 the interaction energy between a peptide and a lipid bilayer (per lipid). The interaction energy is decomposed into electrostatic and van der Waals (vdW) components. As seen from Figure 5 that hIAPPs with four binding orientations have nearly the same vdW interaction energy with lipids, and the electrostatic interaction energy is also similar. However, the electrostatic interaction is much stronger than vdW interaction, indicating that the former plays a dominant role in stabilizing the binding of hIAPP monomer to the POPC lipid bilayer although the net charge of a POPC lipid is zero. Different from our result, a recent MD study by Zhao et al. reported that the electrostatic and vdW interaction energy between hIAPP ion-channel and a DOPC bilayer are quite similar [37].

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