Membrane Binding and Self-Association of the Epsin N-Terminal Homology Domain

Chun Liang Lai, Christine C. Jao, Edward Lyman, Jennifer L. Gallop, Brian J. Peter, Harvey T. McMahon, Ralf Langen, Gregory A. Voth

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Epsin possesses a conserved epsin N-terminal homology (ENTH) domain that acts as a phosphatidylinositol 4,5-bisphosphate-lipid-targeting and membrane-curvature-generating element. Upon binding phosphatidylino-sitol 4,5-bisphosphate, the N-terminal helix (H0) of the ENTH domain becomes structured and aids in the aggregation of ENTH domains, which results in extensive membrane remodeling. In this article, atomistic and coarse-grained (CG) molecular dynamics (MD) simulations are used to investigate the structure and the stability of ENTH domain aggregates on lipid bilayers. EPR experiments are also reported for systems composed of different ENTH-bound membrane morphologies, including membrane vesicles as well as preformed membrane tubules. The EPR data are used to help develop a molecular model of ENTH domain aggregates on preformed lipid tubules that are then studied by CG MD simulation. The combined computational and experimental approach suggests that ENTH domains exist predominantly as monomers on vesiculated structures, while ENTH domains self-associate into dimeric structures and even higher-order oligomers on the membrane tubes. The results emphasize that the arrangement of ENTH domain aggregates depends strongly on whether the local membrane curvature is isotropic or anisotropic. The molecular mechanism of ENTH-domain-induced membrane vesiculation and tubula-tion and the implications of the epsin's role in clathrin-mediated endocytosis resulting from the interplay between ENTH domain membrane binding and ENTH domain self-association are also discussed.

Original languageEnglish (US)
Pages (from-to)800-817
Number of pages18
JournalJournal of Molecular Biology
Volume423
Issue number5
DOIs
StatePublished - Nov 9 2012
Externally publishedYes

Fingerprint

Membranes
Molecular Dynamics Simulation
epsin
Clathrin
Molecular Models
Lipid Bilayers
Membrane Lipids
Phosphatidylinositols
Endocytosis
Lipids

Keywords

  • amphipathic helix binding
  • ENTH domain
  • epsin
  • membrane remodeling
  • molecular dynamics

ASJC Scopus subject areas

  • Molecular Biology

Cite this

Lai, C. L., Jao, C. C., Lyman, E., Gallop, J. L., Peter, B. J., McMahon, H. T., ... Voth, G. A. (2012). Membrane Binding and Self-Association of the Epsin N-Terminal Homology Domain. Journal of Molecular Biology, 423(5), 800-817. https://doi.org/10.1016/j.jmb.2012.08.010

Membrane Binding and Self-Association of the Epsin N-Terminal Homology Domain. / Lai, Chun Liang; Jao, Christine C.; Lyman, Edward; Gallop, Jennifer L.; Peter, Brian J.; McMahon, Harvey T.; Langen, Ralf; Voth, Gregory A.

In: Journal of Molecular Biology, Vol. 423, No. 5, 09.11.2012, p. 800-817.

Research output: Contribution to journalArticle

Lai, CL, Jao, CC, Lyman, E, Gallop, JL, Peter, BJ, McMahon, HT, Langen, R & Voth, GA 2012, 'Membrane Binding and Self-Association of the Epsin N-Terminal Homology Domain', Journal of Molecular Biology, vol. 423, no. 5, pp. 800-817. https://doi.org/10.1016/j.jmb.2012.08.010
Lai, Chun Liang ; Jao, Christine C. ; Lyman, Edward ; Gallop, Jennifer L. ; Peter, Brian J. ; McMahon, Harvey T. ; Langen, Ralf ; Voth, Gregory A. / Membrane Binding and Self-Association of the Epsin N-Terminal Homology Domain. In: Journal of Molecular Biology. 2012 ; Vol. 423, No. 5. pp. 800-817.
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