5W50

Crystal structure of the segment, LIIKGI, from the RRM2 of TDP-43, residues 248-253

5W50 の概要

• エントリーDOI: 10.2210/pdb5w50/pdb
• 分子名称: TAR DNA-binding protein 43 (2 entities in total)
• 機能のキーワード: amyloid, steric zipper, protein fibril
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 1313.76

構造登録者

Guenther, E.L.,Trinh, H.,Sawaya, M.R.,Eisenberg, D.S. (登録日: 2017-06-13, 公開日: 2018-02-21, 最終更新日: 2023-10-04)

主引用文献

Guenther, E.L.,Ge, P.,Trinh, H.,Sawaya, M.R.,Cascio, D.,Boyer, D.R.,Gonen, T.,Zhou, Z.H.,Eisenberg, D.S.
Atomic-level evidence for packing and positional amyloid polymorphism by segment from TDP-43 RRM2.
Nat. Struct. Mol. Biol., 25:311-319, 2018

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 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.

PubMed: 29531287
DOI: 10.1038/s41594-018-0045-5

実験手法

X-RAY DIFFRACTION (1.4 Å)