National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
GM071940
米国
引用
ジャーナル: Nat Struct Mol Biol / 年: 2018 タイトル: Atomic-level evidence for packing and positional amyloid polymorphism by segment from TDP-43 RRM2. 著者: Elizabeth L Guenther / Peng Ge / Hamilton Trinh / Michael R Sawaya / Duilio Cascio / David R Boyer / Tamir Gonen / Z Hong Zhou / David S Eisenberg / 要旨: Proteins in the fibrous amyloid state are a major hallmark of neurodegenerative disease. Understanding the multiple conformations, or polymorphs, of amyloid proteins at the molecular level is a ...Proteins in the fibrous amyloid state are a major hallmark of neurodegenerative disease. Understanding the multiple conformations, or polymorphs, of amyloid proteins at the molecular level is a challenge of amyloid research. Here, we detail the wide range of polymorphs formed by a segment of human TAR DNA-binding protein 43 (TDP-43) as a model for the polymorphic capabilities of pathological amyloid aggregation. Using X-ray diffraction, microelectron diffraction (MicroED) and single-particle cryo-EM, we show that the DLIIKGISVHI segment from the second RNA-recognition motif (RRM2) forms an array of amyloid polymorphs. These associations include seven distinct interfaces displaying five different symmetry classes of steric zippers. Additionally, we find that this segment can adopt three different backbone conformations that contribute to its polymorphic capabilities. The polymorphic nature of this segment illustrates at the molecular level how amyloid proteins can form diverse fibril structures.
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1: TAR DNA-binding protein 43 3: TAR DNA-binding protein 43 2: TAR DNA-binding protein 43 6: TAR DNA-binding protein 43 5: TAR DNA-binding protein 43 4: TAR DNA-binding protein 43 7: TAR DNA-binding protein 43 0: TAR DNA-binding protein 43 8: TAR DNA-binding protein 43
1: TAR DNA-binding protein 43 3: TAR DNA-binding protein 43 2: TAR DNA-binding protein 43 6: TAR DNA-binding protein 43 5: TAR DNA-binding protein 43 4: TAR DNA-binding protein 43 7: TAR DNA-binding protein 43 0: TAR DNA-binding protein 43 8: TAR DNA-binding protein 43
らせん対称: (回転対称性: 1 / Dyad axis: no / N subunits divisor: 1 / Num. of operations: 30 / Rise per n subunits: 1.598 Å / Rotation per n subunits: -120.441 °)