Journal Article

Atomic structures of FUS LC domain segments reveal bases for reversible amyloid fibril formation

Li, Yichen, Li, Dan, Zhao, Minglei, Luo, Feng, Liu, Xiangyu, Li, Xueming, Gui, Xinrui, Zhou, Heng, Liu, Cong, Gu, Jinge

2018

Overview

Thermostable cross-β structures are characteristic of pathological amyloid fibrils, but these structures cannot explain the reversible nature of fibrils formed by RNA-binding proteins such as fused in sarcoma (FUS), involved in RNA granule assembly. Here, we find that two tandem (S/G)Y(S/G) motifs of the human FUS low-complexity domain (FUS LC) form reversible fibrils in a temperature- and phosphorylation-dependent manner. We named these motifs reversible amyloid cores, or RAC1 and RAC2, and determined their atomic structures in fibrillar forms, using microelectron and X-ray diffraction techniques. The RAC1 structure features an ordered-coil fibril spine rather than the extended β-strand typical of amyloids. Ser42, a phosphorylation site of FUS, is critical in the maintenance of the ordered-coil structure, which explains how phosphorylation controls fibril formation. The RAC2 structure shows a labile fibril spine with a wet interface. These structures illuminate the mechanism of reversible fibril formation and dynamic assembly of RNA granules.

• Publisher: Nature Publishing Group
• Subject: Assembly / Coils / Fibrils / FUS protein / Granular materials / Phosphorylation / Proteins / Rac1 protein / Rac2 protein / Ribonucleic acid / RNA / RNA-binding protein / Sarcoma / Spine / Temperature dependence / X-ray diffraction