{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T04:23:38Z","timestamp":1772252618012,"version":"3.50.1"},"reference-count":54,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2022,6,7]],"date-time":"2022-06-07T00:00:00Z","timestamp":1654560000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Science Centre, Poland","award":["#2014\/15\/D\/NZ1\/00968"],"award-info":[{"award-number":["#2014\/15\/D\/NZ1\/00968"]}]},{"name":"European Union\u2019s Horizon 2020 research and innovation programme","award":["#2014\/15\/D\/NZ1\/00968"],"award-info":[{"award-number":["#2014\/15\/D\/NZ1\/00968"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>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 were identified within the HtrA protease family using a non-redundant set (N = 20) of publicly available structures. While the repeats themselves were far from sequence perfect, they had notable conservation to a statistically significant level. Three or more repetitions were identified within each protein despite being statistically expected to randomly occur only once per 1031 residues. This sequence repeat was associated with a six stranded antiparallel \u03b2-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 \u03b2-barrels, but the use of a target human HtrA2 structure showed that these modules had an average RMSD across the set of structures of less than 2 \u212b (mean and median). Our findings support Dayhoff\u2019s hypothesis that complex proteins arose through duplication of simpler peptide motifs and domains.<\/jats:p>","DOI":"10.3390\/biom12060793","type":"journal-article","created":{"date-parts":[[2022,6,9]],"date-time":"2022-06-09T10:49:14Z","timestamp":1654771754000},"page":"793","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The Repeating, Modular Architecture of the HtrA Proteases"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1844-6997","authenticated-orcid":false,"given":"Matthew","family":"Merski","sequence":"first","affiliation":[{"name":"Structural Biology Group, Biological and Chemical Research Centre, Faculty of Chemistry, University of Warsaw, \u017bwirki i Wigury 101, 02-089 Warsaw, Poland"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7698-1170","authenticated-orcid":false,"given":"Sandra","family":"Macedo-Ribeiro","sequence":"additional","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade and Instituto de Biologia Molecular e Celular (IBMC), Universidade do Porto, 4200-135 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0172-8063","authenticated-orcid":false,"given":"Rafal M.","family":"Wieczorek","sequence":"additional","affiliation":[{"name":"Faculty of Chemistry, University of Warsaw, Pasteura 1, 02-093 Warsaw, Poland"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1769-4542","authenticated-orcid":false,"given":"Maria W.","family":"G\u00f3rna","sequence":"additional","affiliation":[{"name":"Structural Biology Group, Biological and Chemical Research Centre, Faculty of Chemistry, University of Warsaw, \u017bwirki i Wigury 101, 02-089 Warsaw, Poland"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Rad\u00f3-Trilla, N., and Alb\u00e0, M. 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