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bioRxiv · 10.1101/2022.04.28.489847

The Repeating, Modular Architecture of the HtrA Proteases

Merski, M.·Macedo-Ribeiro, S.·Wieczorek, R. M.·Gorna, M. W.
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Abstract

A conserved, 26 residue sequence [AA(X2)[A/G][G/L](X2)GDV[I/L](X2)[V/L]NGE(X1)V(X6)] and corresponding structure repeating module was identified within the HtrA protease family using a non-redundant set (N=20) of publically available structures. While the repeats themselves were far from sequence perfect they had notable conservation to a statistically significant level with three or more repetitions identified within one protein at a level that would be expected to randomly occur only once per 1031 residues. This sequence repeat was associated with a six stranded antiparallel {beta}-barrel module, two of which 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 domains. Automated structural alignment methods had difficulties in superimposing these {beta}-barrels but use of a target human HtrA2 structure showed that these modules had an average RMSD across the set of structures of less than 2 [A] (mean and median). Our findings support Dayhoffs hypothesis that complex proteins arose through duplication of simpler peptide motifs and domains.

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Merski, M., Macedo-Ribeiro, S., Wieczorek, R. M., Gorna, M. W.. 2022-04-29. The Repeating, Modular Architecture of the HtrA Proteases. https://doi.org/10.1101/2022.04.28.489847

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