Binsen Li / Peng Ge / Kevin A Murray / Phorum Sheth / Meng Zhang / Gayatri Nair / Michael R Sawaya / Woo Shik Shin / David R Boyer / Shulin Ye / David S Eisenberg / Z Hong Zhou / Lin Jiang /
PubMed Abstract
α-Synuclein (aSyn) fibrillar polymorphs have distinct in vitro and in vivo seeding activities, contributing differently to synucleinopathies. Despite numerous prior attempts, how polymorphic aSyn ...α-Synuclein (aSyn) fibrillar polymorphs have distinct in vitro and in vivo seeding activities, contributing differently to synucleinopathies. Despite numerous prior attempts, how polymorphic aSyn fibrils differ in atomic structure remains elusive. Here, we present fibril polymorphs from the full-length recombinant human aSyn and their seeding capacity and cytotoxicity in vitro. By cryo-electron microscopy helical reconstruction, we determine the structures of the two predominant species, a rod and a twister, both at 3.7 Å resolution. Our atomic models reveal that both polymorphs share a kernel structure of a bent β-arch, but differ in their inter-protofilament interfaces. Thus, different packing of the same kernel structure gives rise to distinct fibril polymorphs. Analyses of disease-related familial mutations suggest their potential contribution to the pathogenesis of synucleinopathies by altering population distribution of the fibril polymorphs. Drug design targeting amyloid fibrils in neurodegenerative diseases should consider the formation and distribution of concurrent fibril polymorphs.
Oct 5, 2021. Nobel Prize for mechanically activated and temperature-gated ion channels
Nobel Prize for mechanically activated and temperature-gated ion channels
The Nobel Prize in Physiology or Medicine 2021 was awarded jointly to David Julius and Ardem Patapoutian "for their discoveries of receptors for temperature and touch."
EM Navigator can help to find cryo-EM structure data by both pioneers.
In the structure databanks used in Yorodumi, some data are registered as the other names, "COVID-19 virus" and "2019-nCoV". Here are the details of the virus and the list of structure data.
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homo sapiens (human)
