Publication

Molecular mechanism for bidirectional regulation of CD44 for lipid raft affiliation by palmitoylations and PIP2

Sun, F., Schroer, C. F. E., Palacios, C. R., Xu, L., Luo, S-Z. & Marrink, S. J., 9-Apr-2020, In : PLoS Computational Biology. 16, 4, 20 p., e1007777.

Research output: Contribution to journalArticleAcademicpeer-review

APA

Sun, F., Schroer, C. F. E., Palacios, C. R., Xu, L., Luo, S-Z., & Marrink, S. J. (2020). Molecular mechanism for bidirectional regulation of CD44 for lipid raft affiliation by palmitoylations and PIP2. PLoS Computational Biology, 16(4), [e1007777]. https://doi.org/10.1371/journal.pcbi.1007777

Author

Sun, Fude ; Schroer, Carsten F E ; Palacios, Carlos R ; Xu, Lida ; Luo, Shi-Zhong ; Marrink, Siewert J. / Molecular mechanism for bidirectional regulation of CD44 for lipid raft affiliation by palmitoylations and PIP2. In: PLoS Computational Biology. 2020 ; Vol. 16, No. 4.

Harvard

Sun, F, Schroer, CFE, Palacios, CR, Xu, L, Luo, S-Z & Marrink, SJ 2020, 'Molecular mechanism for bidirectional regulation of CD44 for lipid raft affiliation by palmitoylations and PIP2', PLoS Computational Biology, vol. 16, no. 4, e1007777. https://doi.org/10.1371/journal.pcbi.1007777

Standard

Molecular mechanism for bidirectional regulation of CD44 for lipid raft affiliation by palmitoylations and PIP2. / Sun, Fude; Schroer, Carsten F E; Palacios, Carlos R; Xu, Lida; Luo, Shi-Zhong; Marrink, Siewert J.

In: PLoS Computational Biology, Vol. 16, No. 4, e1007777, 09.04.2020.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

Sun F, Schroer CFE, Palacios CR, Xu L, Luo S-Z, Marrink SJ. Molecular mechanism for bidirectional regulation of CD44 for lipid raft affiliation by palmitoylations and PIP2. PLoS Computational Biology. 2020 Apr 9;16(4). e1007777. https://doi.org/10.1371/journal.pcbi.1007777


BibTeX

@article{b01c5e7734fd4709ac3f3c64fdfc97c7,
title = "Molecular mechanism for bidirectional regulation of CD44 for lipid raft affiliation by palmitoylations and PIP2",
abstract = "The co-localization of Cluster-of-Differentiation-44 protein (CD44) and cytoplasmic adaptors in specific membrane environments is crucial for cell adhesion and migration. The process is controlled by two different pathways: On the one hand palmitoylation keeps CD44 in lipid raft domains and disables the linking to the cytoplasmic adaptor, whereas on the other hand, the presence of phosphatidylinositol-4,5-biphosphate (PIP2) lipids accelerates the formation of the CD44-adaptor complex. The molecular mechanism explaining how CD44 is migrating into and out of the lipid raft domains and its dependence on both palmitoylations and the presence of PIP2 remains, however, elusive. In this study, we performed extensive molecular dynamics simulations to study the raft affinity and translocation of CD44 in phase separated model membranes as well as more realistic plasma membrane environments. We observe a delicate balance between the influence of the palmitoylations and the presence of PIP2 lipids: whereas the palmitoylations of CD44 increases the affinity for raft domains, PIP2 lipids have the opposite effect. Additionally, we studied the association between CD44 and the membrane adaptor FERM in dependence of these factors. We find that the presence of PIP2 lipids allows CD44 and FERM to associate in an experimentally observed binding mode whereas the highly palmitoylated species shows no binding affinity. Together, our results shed light on the sophisticated mechanism on how membrane translocation and peripheral protein association can be controlled by both protein modifications and membrane composition.",
keywords = "MARTINI FORCE-FIELD, PHOSPHATIDYLINOSITOL, 4,5-BISPHOSPHATE, COMPUTATIONAL LIPIDOMICS, CYTOPLASMIC DOMAIN, L-SELECTIN, DYNAMICS, PROTEINS, INSIGHTS, ASSOCIATION, SITES",
author = "Fude Sun and Schroer, {Carsten F E} and Palacios, {Carlos R} and Lida Xu and Shi-Zhong Luo and Marrink, {Siewert J}",
year = "2020",
month = apr,
day = "9",
doi = "10.1371/journal.pcbi.1007777",
language = "English",
volume = "16",
journal = "PLoS Computational Biology",
issn = "1553-7358",
publisher = "PUBLIC LIBRARY SCIENCE",
number = "4",

}

RIS

TY - JOUR

T1 - Molecular mechanism for bidirectional regulation of CD44 for lipid raft affiliation by palmitoylations and PIP2

AU - Sun, Fude

AU - Schroer, Carsten F E

AU - Palacios, Carlos R

AU - Xu, Lida

AU - Luo, Shi-Zhong

AU - Marrink, Siewert J

PY - 2020/4/9

Y1 - 2020/4/9

N2 - The co-localization of Cluster-of-Differentiation-44 protein (CD44) and cytoplasmic adaptors in specific membrane environments is crucial for cell adhesion and migration. The process is controlled by two different pathways: On the one hand palmitoylation keeps CD44 in lipid raft domains and disables the linking to the cytoplasmic adaptor, whereas on the other hand, the presence of phosphatidylinositol-4,5-biphosphate (PIP2) lipids accelerates the formation of the CD44-adaptor complex. The molecular mechanism explaining how CD44 is migrating into and out of the lipid raft domains and its dependence on both palmitoylations and the presence of PIP2 remains, however, elusive. In this study, we performed extensive molecular dynamics simulations to study the raft affinity and translocation of CD44 in phase separated model membranes as well as more realistic plasma membrane environments. We observe a delicate balance between the influence of the palmitoylations and the presence of PIP2 lipids: whereas the palmitoylations of CD44 increases the affinity for raft domains, PIP2 lipids have the opposite effect. Additionally, we studied the association between CD44 and the membrane adaptor FERM in dependence of these factors. We find that the presence of PIP2 lipids allows CD44 and FERM to associate in an experimentally observed binding mode whereas the highly palmitoylated species shows no binding affinity. Together, our results shed light on the sophisticated mechanism on how membrane translocation and peripheral protein association can be controlled by both protein modifications and membrane composition.

AB - The co-localization of Cluster-of-Differentiation-44 protein (CD44) and cytoplasmic adaptors in specific membrane environments is crucial for cell adhesion and migration. The process is controlled by two different pathways: On the one hand palmitoylation keeps CD44 in lipid raft domains and disables the linking to the cytoplasmic adaptor, whereas on the other hand, the presence of phosphatidylinositol-4,5-biphosphate (PIP2) lipids accelerates the formation of the CD44-adaptor complex. The molecular mechanism explaining how CD44 is migrating into and out of the lipid raft domains and its dependence on both palmitoylations and the presence of PIP2 remains, however, elusive. In this study, we performed extensive molecular dynamics simulations to study the raft affinity and translocation of CD44 in phase separated model membranes as well as more realistic plasma membrane environments. We observe a delicate balance between the influence of the palmitoylations and the presence of PIP2 lipids: whereas the palmitoylations of CD44 increases the affinity for raft domains, PIP2 lipids have the opposite effect. Additionally, we studied the association between CD44 and the membrane adaptor FERM in dependence of these factors. We find that the presence of PIP2 lipids allows CD44 and FERM to associate in an experimentally observed binding mode whereas the highly palmitoylated species shows no binding affinity. Together, our results shed light on the sophisticated mechanism on how membrane translocation and peripheral protein association can be controlled by both protein modifications and membrane composition.

KW - MARTINI FORCE-FIELD

KW - PHOSPHATIDYLINOSITOL

KW - 4,5-BISPHOSPHATE

KW - COMPUTATIONAL LIPIDOMICS

KW - CYTOPLASMIC DOMAIN

KW - L-SELECTIN

KW - DYNAMICS

KW - PROTEINS

KW - INSIGHTS

KW - ASSOCIATION

KW - SITES

U2 - 10.1371/journal.pcbi.1007777

DO - 10.1371/journal.pcbi.1007777

M3 - Article

C2 - 32271757

VL - 16

JO - PLoS Computational Biology

JF - PLoS Computational Biology

SN - 1553-7358

IS - 4

M1 - e1007777

ER -

ID: 122517907