Aβ1-25-Derived Sphingolipid-Domain Tracer Peptide SBD Interacts with Membrane Ganglioside Clusters via a Coil-Helix-Coil Motif
The Amyloid-β (Aβ)-derived, sphingolipid binding domain (SBD) peptide is a fluorescently tagged probe used to trace the diffusion behavior of sphingolipid-containing microdomains in cell membranes through binding to a constellation of glycosphingolipids, sphingomyelin, and cholesterol. However, the...
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doaj-7b22b0df10554007a375cad5b2072f652020-11-24T21:46:02ZengMDPI AGInternational Journal of Molecular Sciences1422-00672015-11-011611263182633210.3390/ijms161125955ijms161125955Aβ1-25-Derived Sphingolipid-Domain Tracer Peptide SBD Interacts with Membrane Ganglioside Clusters via a Coil-Helix-Coil MotifYaofeng Wang0Rachel Kraut1Yuguang Mu2School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, 637551 Singapore, SingaporeSchool of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, 637551 Singapore, SingaporeSchool of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, 637551 Singapore, SingaporeThe Amyloid-β (Aβ)-derived, sphingolipid binding domain (SBD) peptide is a fluorescently tagged probe used to trace the diffusion behavior of sphingolipid-containing microdomains in cell membranes through binding to a constellation of glycosphingolipids, sphingomyelin, and cholesterol. However, the molecular details of the binding mechanism between SBD and plasma membrane domains remain unclear. Here, to investigate how the peptide recognizes the lipid surface at an atomically detailed level, SBD peptides in the environment of raft-like bilayers were examined in micro-seconds-long molecular dynamics simulations. We found that SBD adopted a coil-helix-coil structural motif, which binds to multiple GT1b gangliosides via salt bridges and CH–π interactions. Our simulation results demonstrate that the CH–π and electrostatic forces between SBD monomers and GT1b gangliosides clusters are the main driving forces in the binding process. The presence of the fluorescent dye and linker molecules do not change the binding mechanism of SBD probes with gangliosides, which involves the helix-turn-helix structural motif that was suggested to constitute a glycolipid binding domain common to some sphingolipid interacting proteins, including HIV gp120, prion, and Aβ.http://www.mdpi.com/1422-0067/16/11/25955Sphingolipid binding domainlipid raftsmolecular dynamics simulation |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yaofeng Wang Rachel Kraut Yuguang Mu |
spellingShingle |
Yaofeng Wang Rachel Kraut Yuguang Mu Aβ1-25-Derived Sphingolipid-Domain Tracer Peptide SBD Interacts with Membrane Ganglioside Clusters via a Coil-Helix-Coil Motif International Journal of Molecular Sciences Sphingolipid binding domain lipid rafts molecular dynamics simulation |
author_facet |
Yaofeng Wang Rachel Kraut Yuguang Mu |
author_sort |
Yaofeng Wang |
title |
Aβ1-25-Derived Sphingolipid-Domain Tracer Peptide SBD Interacts with Membrane Ganglioside Clusters via a Coil-Helix-Coil Motif |
title_short |
Aβ1-25-Derived Sphingolipid-Domain Tracer Peptide SBD Interacts with Membrane Ganglioside Clusters via a Coil-Helix-Coil Motif |
title_full |
Aβ1-25-Derived Sphingolipid-Domain Tracer Peptide SBD Interacts with Membrane Ganglioside Clusters via a Coil-Helix-Coil Motif |
title_fullStr |
Aβ1-25-Derived Sphingolipid-Domain Tracer Peptide SBD Interacts with Membrane Ganglioside Clusters via a Coil-Helix-Coil Motif |
title_full_unstemmed |
Aβ1-25-Derived Sphingolipid-Domain Tracer Peptide SBD Interacts with Membrane Ganglioside Clusters via a Coil-Helix-Coil Motif |
title_sort |
aβ1-25-derived sphingolipid-domain tracer peptide sbd interacts with membrane ganglioside clusters via a coil-helix-coil motif |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1422-0067 |
publishDate |
2015-11-01 |
description |
The Amyloid-β (Aβ)-derived, sphingolipid binding domain (SBD) peptide is a fluorescently tagged probe used to trace the diffusion behavior of sphingolipid-containing microdomains in cell membranes through binding to a constellation of glycosphingolipids, sphingomyelin, and cholesterol. However, the molecular details of the binding mechanism between SBD and plasma membrane domains remain unclear. Here, to investigate how the peptide recognizes the lipid surface at an atomically detailed level, SBD peptides in the environment of raft-like bilayers were examined in micro-seconds-long molecular dynamics simulations. We found that SBD adopted a coil-helix-coil structural motif, which binds to multiple GT1b gangliosides via salt bridges and CH–π interactions. Our simulation results demonstrate that the CH–π and electrostatic forces between SBD monomers and GT1b gangliosides clusters are the main driving forces in the binding process. The presence of the fluorescent dye and linker molecules do not change the binding mechanism of SBD probes with gangliosides, which involves the helix-turn-helix structural motif that was suggested to constitute a glycolipid binding domain common to some sphingolipid interacting proteins, including HIV gp120, prion, and Aβ. |
topic |
Sphingolipid binding domain lipid rafts molecular dynamics simulation |
url |
http://www.mdpi.com/1422-0067/16/11/25955 |
work_keys_str_mv |
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