Atomic-level evidence for packing and positional amyloid polymorphism by segment from TDP-43 RRM2.

ABSTRACT: 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 ²⁴⁷DLIIKGISVHI²⁵⁷ 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

SUBMITTER: Guenther EL 

PROVIDER: S-EPMC6056015 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature