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Mechanisms of Membrane Pore Formation by Amyloidogenic Peptides in Amyotrophic Lateral Sclerosis
Author(s) -
Chen Charles H.,
Khan Ayesha,
Huang Joseph JenTse,
Ulmschneider Martin B.
Publication year - 2016
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201601765
Subject(s) - lipid bilayer , biophysics , membrane , bilayer , molecular dynamics , chemistry , cytotoxicity , chemical physics , biochemistry , computational chemistry , biology , in vitro
Using unbiased atomic‐detailed molecular dynamics simulations, the C‐terminal fragments of TDP‐43 are observed to aggregate and form disordered‐toroidal pores in a lipid bilayer. Cytotoxicity of TDP‐43 may be inferred from the observation that the membrane pores catalyze lipid flip‐flop between bilayer leaflets and conduct water at high rates.