An allosteric HTRA1-calpain 2 complex with restricted activation profile
| Autor: | Juliana Rey, Maike Breiden, Vanda Lux, Anika Bluemke, Maike Steindel, Kamilla Ripkens, Bastian Möllers, Kenny Bravo Rodriguez, Prisca Boisguerin, Rudolf Volkmer, Joel Mieres-Perez, Tim Clausen, Elsa Sanchez-Garcia, Michael Ehrmann |
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| Přispěvatelé: | Universität Duisburg-Essen [Essen], Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Cardiff University, MORNET, Dominique |
| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
Amyloid
HTRA1 Multidisciplinary Calpain Serine Endopeptidases Medizin High-Temperature Requirement A Serine Peptidase 1 Serine protease Proteolysis [SDV.BBM] Life Sciences [q-bio]/Biochemistry Molecular Biology [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology Serine Proteases Tau Allostery Biologie Amyloid fibrils |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America Proceedings of the National Academy of Sciences of the United States of America, 2022, 119 (14), pp.e2113520119. ⟨10.1073/pnas.2113520119⟩ |
| ISSN: | 0027-8424 1091-6490 |
| DOI: | 10.1073/pnas.2113520119⟩ |
| Popis: | Significance Classic serine proteases are synthesized as inactive precursors that are proteolytically processed, resulting in irreversible activation. We report an alternative and reversible mechanism of activation that is executed by an inactive protease. This mechanism involves a protein complex between the serine protease HTRA1 and the cysteine protease calpain 2. Surprisingly, activation is restricted as it improves the proteolysis of soluble tau protein but not the dissociation and degradation of its amyloid fibrils, a task that free HTRA1 is efficiently performing. These data exemplify a challenge for protein quality control proteases in the clearing of pathogenic fibrils and suggest a potential for unexpected side effects of chemical modulators targeting PDZ or other domains located at a distance to the active site. |
| Databáze: | OpenAIRE |
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