Structural insights into the activation mechanisms of human HtrA serine proteases

Dorota Żurawa-Janicka , Tomasz Wenta , Mirosław Jarząb , Joanna Skórko-Glonek , Przemysław Glaza , Artur Giełdoń , Jerzy Ciarkowski , Barbara Lipińska

Abstract

Human HtrA1-4 proteins belong to the HtrA family of evolutionarily conserved serine proteases and function as important modulators of many physiological processes, including maintenance of mitochondrial homeostasis, cell signaling and apoptosis. Disturbances in their action are linked to severe diseases, including oncogenesis and neurodegeneration. The HtrA1-4 proteins share structural and functional features of other members of the HtrA protein family, however there are several significant differences in structural architecture and mechanisms of action which makes each of them unique. Our goal is to present recent studies regarding human HtrAs. We focus on their physiological functions, structure and regulation, and describe current models of activation mechanisms. Knowledge of molecular basis of the human HtrAs' action is a subject of great interest; it is crucial for understanding their relevance in cellular physiology and pathogenesis as well as for using them as targets in future therapies of diseases such as neurodegenerative disorders and cancer.
Author Dorota Żurawa-Janicka KBOiM
Dorota Żurawa-Janicka,,
- Department of Biochemistry
, Tomasz Wenta KBOiM
Tomasz Wenta,,
- Department of Biochemistry
, Mirosław Jarząb KBOiM
Mirosław Jarząb,,
- Department of Biochemistry
, Joanna Skórko-Glonek KBOiM
Joanna Skórko-Glonek,,
- Department of Biochemistry
, Przemysław Glaza KBOiM
Przemysław Glaza,,
- Department of Biochemistry
, Artur Giełdoń PSP
Artur Giełdoń,,
- Laboratory of Simulation of Polymers
, Jerzy Ciarkowski PMM
Jerzy Ciarkowski,,
- Laboratory of Molecular Modeling
, Barbara Lipińska KBOiM
Barbara Lipińska,,
- Department of Biochemistry
Journal seriesArchives of Biochemistry and Biophysics, ISSN 0003-9861
Issue year2017
Vol621
Pages6-23
Publication size in sheets0.85
Keywords in EnglishHtrA proteins, serine proteases, allosteric regulation, PDZ domain
DOIDOI:10.1016/j.abb.2017.04.004
URL http://doi.org/10.1016/j.abb.2017.04.004
Languageen angielski
Score (nominal)30
ScoreMinisterial score = 30.0, 20-12-2017, ArticleFromJournal
Ministerial score (2013-2016) = 30.0, 20-12-2017, ArticleFromJournal
Publication indicators WoS Impact Factor: 2016 = 3.165 (2) - 2016=2.974 (5)
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