Alexander Barrett

Abstract Multiple neurodegenerative diseases are characterized by aberrant proteinaceous accumulations of tau. Here, we report a RING-in-between-RING-type E3 ligase, TRIAD3A, that functions as an autophagy adaptor for tau. TRIAD3A(RNF216) is an essential gene with mutations causing age-progressive neurodegeneration. Our studies reveal that TRIAD3A E3 ligase catalyses mixed K11/K63 polyubiquitin chains and self-assembles into liquid–liquid phase separated (LLPS) droplets.

Lauren R. Schmitt‡, Rachel Henderson§, Alexander Barrett‡, Zsuzsanna Darula¶, Aaron Issaian‡, Angelo D'Alessandro‡, Nathan Clendenen§ and Kirk C. Hansen‡1 From the Departments of ‡Biochemistry and Molecular Genetics and §Anesthesiology, University of Colorado School of Medicine, Aurora, Colorado 80045 and ¶Laboratory of Proteomics Research, Biological Research Center of the Hungarian Academy of Sciences, H-6701 Szeged, Hungary ↵1 To whom correspondence should be addressed.

The roles of factor XIIIa–specific cross-links in thrombus formation, regression, or probability for embolization are largely unknown. A molecular understanding of fibrin architecture at the level of these cross-links could inform the development of therapeutic strategies to prevent the sequelae of thromboembolism. Here, we present an MS-based method to map native factor XIIIa cross-links in the insoluble matrix component of whole-blood or plasma-fibrin clots and in in vivo thrombi.