CryoEM structure of the low-complexity domain of hnRNPA2 and its conversion to pathogenic amyloid

Abstract

hnRNPA2 is involved in RNA metabolism and can form both functional amyloid-like fibrils in membraneless organelles, and pathogenic fibrils in neurodegenerative conditions. Here, the authors present the cryo-EM fibril structure of the wild-type hnRNPA2 low-complexity domain (LCD) and the crystal structure of a LCD segment with the disease causing D290V variant and discuss how mutations can transform fibril structure from a functional to a pathogenic form.