ALS mutations disrupt self-association between the ubiquilin STI1 hydrophobic groove and internal placeholder sequences
Joan Onwunma·Matthew L. Wohlever·Saeed A. Binsabaan·S. Allen·Deepika Gaur·Sachini Thanthirige·Banumathi Sankaran
Ubiquilins are molecular chaperones that play multifaceted roles in proteostasis, with point mutations in UBQLN2 leading to altered phase-separation properties and amyotrophic lateral sclerosis (ALS). Our mechanistic understanding of this essential process has been hindered by a lack of structural information on the STI1 domain, which is essential for ubiquilin chaperone activity and phase separation. Here, we present the first crystal structure of a ubiquilin-family STI1 domain bound to a trans