The role of the LB structural loop and its interactions with the PDZ domain of the human HtrA3 protease

Tomasz Wenta , Przemysław Glaza , Mirosław Jarząb , Urszula Zarzecka , Dorota Żurawa-Janicka , Adam Lesner , Joanna Skórko-Glonek , Barbara Lipińska


Human HtrA3 protease is a proapoptotic protein, involved in embryo implantation and oncogenesis. In stress conditions the protease is activated by removal of its N-terminal domain. The activated form, ΔN-HtrA3L is a homotrimer composed of the protease (PD) and PDZ domains. The LB structural loop of the PD is longer by six amino acid residues than its counterparts of other human HtrA proteins and interacts with the PDZ in a way not observed in other known HtrA structures. By size exclusion chromatography of the ΔN-HtrA3L mutated variants we found that removal of the additional LB loop residues caused a complete loss of the proper trimeric structure while impairing their interactions with the PDZ domain decreased the amount of the trimers. This indicates that the LB loop participates in stabilization of the ΔN-HtrA3L oligomer structure and suggests involvement of the LB-PDZ interactions in the stabilization. Removal of the additional LB loop residues impaired the ΔN-HtrA3L activity against the peptide and protein substrates, including the antiapoptotic XIAP protein, while a decrease in the LB-PDZ interaction caused a diminished efficiency of the peptide cleavage. These results indicate that the additional LB residues are important for the ΔN-HtrA3L proteolytic activity. Furthermore, a monomeric form of the ΔN-HtrA3L is proteolytically inactive. In conclusion, our results suggest that the expanded LB loop promotes the ΔN-HtrA3L activity by stabilizing the protease native trimeric structure.
Author Tomasz Wenta (FB / DB)
Tomasz Wenta,,
- Department of Biochemistry
, Przemysław Glaza (FB / DB)
Przemysław Glaza,,
- Department of Biochemistry
, Mirosław Jarząb (FB / DB)
Mirosław Jarząb,,
- Department of Biochemistry
, Urszula Zarzecka (FB / DB)
Urszula Zarzecka,,
- Department of Biochemistry
, Dorota Żurawa-Janicka (FB / DB)
Dorota Żurawa-Janicka,,
- Department of Biochemistry
, Adam Lesner (FCh / DET / LBAN)
Adam Lesner,,
- Laboratory of Biochemical Analytics and Nanodiagnostics
, Joanna Skórko-Glonek (FB / DB)
Joanna Skórko-Glonek,,
- Department of Biochemistry
, Barbara Lipińska (FB / DB)
Barbara Lipińska,,
- Department of Biochemistry
Journal seriesBiochimica et Biophysica Acta (BBA) - Proteins and Proteomics, ISSN 1570-9639, (A 30 pkt)
Issue year2017
Publication size in sheets0.5
Keywords in EnglishHtrA proteins, human HtrA3 protease, LB loop, human HtrA3 activity, XIAP proteolysis
Languageen angielski
Score (nominal)30
ScoreMinisterial score = 30.0, ArticleFromJournal
Ministerial score (2013-2016) = 30.0, ArticleFromJournal
Publication indicators WoS Citations = 8; WoS Impact Factor: 2017 = 2.609 (2) - 2017=2.848 (5); Scopus Citations = 8
Citation count*10 (2020-05-30)
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* presented citation count is obtained through Internet information analysis and it is close to the number calculated by the Publish or Perish system.
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