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@article{guerrero-ferreira_two_2019,
title = {Two new polymorphic structures of human full-length alpha-synuclein fibrils solved by cryo-electron microscopy},
volume = {8},
issn = {2050-084X},
url = {https://doi.org/10.7554/eLife.48907},
doi = {10.7554/eLife.48907},
abstract = {Intracellular inclusions rich in alpha-synuclein are a hallmark of several neuropathological diseases including Parkinson's disease ({PD}). Previously, we reported the structure of alpha-synuclein fibrils (residues 1-121), composed of two protofibrils that are connected via a densely-packed interface formed by residues 50-57 (Guerrero-Ferreira, {eLife} 218;7:e36402). We here report two new polymorphic atomic structures of alpha-synuclein fibrils termed polymorphs 2a and 2b, at 3.0 Å and 3.4 Å resolution, respectively. These polymorphs show a radically different structure compared to previously reported polymorphs. The new structures have a 10 nm fibril diameter and are composed of two protofilaments which interact via intermolecular salt-bridges between amino acids K45, E57 (polymorph 2a) or E46 (polymorph 2b). The non-amyloid component ({NAC}) region of alpha-synuclein is fully buried by previously non-described interactions with the N-terminus. A hydrophobic cleft, the location of familial {PD} mutation sites, and the nature of the protofilament interface now invite to formulate hypotheses about fibril formation, growth and stability.},
pages = {e48907},
journaltitle = {{eLife}},
author = {Guerrero-Ferreira, Ricardo and Taylor, Nicholas {MI} and Arteni, Ana-Andreea and Kumari, Pratibha and Mona, Daniel and Ringler, Philippe and Britschgi, Markus and Lauer, Matthias E and Makky, Ali and Verasdonck, Joeri and Riek, Roland and Melki, Ronald and Meier, Beat H and Böckmann, Anja and Bousset, Luc and Stahlberg, Henning},
editor = {Scheres, Sjors {HW}},
urldate = {2019-12-10},
date = {2019-12-09},
keywords = {highlight, peer-reviewed},
}