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| Title | Atomic-level evidence for packing and positional amyloid polymorphism by segment from TDP-43 RRM2. |
|---|---|
| Journal, issue, pages | Nat Struct Mol Biol, Vol. 25, Issue 4, Page 311-319, Year 2018 |
| Publish date | Mar 12, 2018 |
 Authors | Elizabeth L Guenther / Peng Ge / Hamilton Trinh / Michael R Sawaya / Duilio Cascio / David R Boyer / Tamir Gonen / Z Hong Zhou / David S Eisenberg /  |
| PubMed 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 ...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. |
 External links | Nat Struct Mol Biol / PubMed:29531287 / PubMed Central |
| Methods | EM (electron crystallography) / EM (helical sym.) / X-ray diffraction |
| Resolution | 1.4 - 3.8 Å |
| Structure data | EMDB-8765, PDB-5w52: EMDB-8781, PDB-5w7v:  PDB-5w50: |
| Chemicals |  ChemComp-HOH: |
| Source |
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 Keywords | PROTEIN FIBRIL /  Amyloid / steric zipper |
