Protease domains arise from repeats

The Repeating, Modular Architecture of the HtrA Proteases.

Merski M, Macedo-Ribeiro S, Wieczorek RM, Górna MW

Biomolecules (2022) 12(6), 793 https://doi.org/10.3390/biom12060793

We identify a repeating module conserved within the HtrA protease family as a 26-residue sequence motif [AA(X₂)[A/G][G/L](X₂)GDV[I/L](X₂)[V/L]NGE(X₁)V(X₆)] and the corresponding structure associated with a six-stranded antiparallel β-barrel module. Two β-barrel modules are present in the core of the structures of the PA clan of serine proteases, while a modified version of this module could be identified in the PDZ-like domain. Our findings support Dayhoff’s hypothesis that complex proteins arose through duplication of simpler peptide motifs and domains.

These results were obtained using our method of detecting repeat proteins developed in the course of SONATA project (#2014/15/D/NZ1/00968) supported by the National Science Centre, Poland.