title: Structural insights into the activation mechanisms of human HtrA serine proteases.
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.
authors.affiliation: Department of General and Medical Biochemistry, Faculty of Biology, University of Gdansk, Wita Stwosza 59, 80-308 Gdansk, Poland. Electronic address: dorota.zurawa@biol.ug.edu.pl.
authors.forename: Dorota
authors.initials: D
authors.lastname: Zurawa-Janicka
authors.affiliation: Department of General and Medical Biochemistry, Faculty of Biology, University of Gdansk, Wita Stwosza 59, 80-308 Gdansk, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Wenta
authors.affiliation: Department of General and Medical Biochemistry, Faculty of Biology, University of Gdansk, Wita Stwosza 59, 80-308 Gdansk, Poland.
authors.forename: Miroslaw
authors.initials: M
authors.lastname: Jarzab
authors.affiliation: Department of General and Medical Biochemistry, Faculty of Biology, University of Gdansk, Wita Stwosza 59, 80-308 Gdansk, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Skorko-Glonek
authors.affiliation: Department of General and Medical Biochemistry, Faculty of Biology, University of Gdansk, Wita Stwosza 59, 80-308 Gdansk, Poland.
authors.forename: Przemyslaw
authors.initials: P
authors.lastname: Glaza
authors.affiliation: Department of Theoretical Chemistry, Faculty of Chemistry, University of Gdansk, Wita Stwosza 63, 80-308 Gdansk, Poland.
authors.forename: Artur
authors.initials: A
authors.lastname: Gieldon
authors.affiliation: Department of Theoretical Chemistry, Faculty of Chemistry, University of Gdansk, Wita Stwosza 63, 80-308 Gdansk, Poland.
authors.forename: Jerzy
authors.initials: J
authors.lastname: Ciarkowski
authors.affiliation: Department of General and Medical Biochemistry, Faculty of Biology, University of Gdansk, Wita Stwosza 59, 80-308 Gdansk, Poland.
authors.forename: Barbara
authors.initials: B
authors.lastname: Lipinska
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D001665:Binding Sites; D004789:Enzyme Activation; D006801:Humans; D008928:Mitochondria / Q000502:physiology*; D054731:PDZ Domains / Q000502:physiology; D011485:Protein Binding; D011487:Protein Conformation; D012697:Serine Endopeptidases / Q000737:chemistry* / Q000378:metabolism* / Q000648:ultrastructure; D015398:Signal Transduction / Q000502:physiology*; D013329:Structure-Activity Relationship
chemical_list: D012697:Serine Endopeptidases
keywords: Allosteric regulation; HtrA proteins; PDZ domain; Serine proteases