Figure 1

Sequence alignment and prediction of aggregation-prone regions of C-terminal ubiquilin constructs (UBQLN1^438–589, UBQLN2^430–624, and UBQLN4^444–601) used for in vitro studies. (a) The UBA domains are highly conserved (93% identical) with the major sequence differences residing in the region between STI1-4 and UBA^30,51. Identical residues are colored in red. (b) Zipper DB was used to predict regions that may drive aggregation of ubiquilin constructs³¹. In the histogram, each bar represents a six-residue-long segment. Segments with Rosetta energies smaller than − 23 kcal/mol (black line) are predicted to form β-sheet structures characteristic of amyloids, and are colored in red. In orange are the segments where Rosetta energies are between − 22 and − 23 kcal/mol, a unit larger than the threshold of − 23 kcal/mol. As with the sequence alignment, the aggregation profiles of these ubiquilin constructs differ mainly in the region between STI1-4 and the UBA domain. The UBQLN2 PXX repeat motif is not shown because none of its segments were predicted to form β-sheet structures. Asterisks designate the gaps in the multiple sequence alignment of the ubiquilins.