Please use this identifier to cite or link to this item:
http://doi.org/10.25358/openscience-9911
Authors: | Felten, Matthias Distler, Ute Wiegen, Nele von Łacki, Mateusz Behl, Christian Tenzer, Stefan Stöcker, Walter Körschgen, Hagen |
Title: | Substrate profiling of the metalloproteinase ovastacin uncovers specific enzyme–substrate interactions and discloses fertilization-relevant substrates |
Online publication date: | 8-Jan-2024 |
Year of first publication: | 2023 |
Language: | english |
Abstract: | The metalloproteinase ovastacin is released by the mammalian egg upon fertilization and cleaves a distinct peptide bond in zona pellucida protein 2 (ZP2), a component of the enveloping extracellular matrix. This limited proteolysis causes zona pellucida hardening, abolishes sperm binding, and thereby regulates fertility. Accordingly, this process is tightly controlled by the plasma protein fetuin-B, an endogenous competitive inhibitor. At present, little is known about how the cleavage characteristics of ovastacin differ from closely related proteases. Physiological implications of ovastacin beyond ZP2 cleavage are still obscure. In this study, we employed N-terminal amine isotopic labeling of substrates (N-TAILS) contained in the secretome of mouse embryonic fibroblasts to elucidate the substrate specificity and the precise cleavage site specificity. Furthermore, we were able to unravel the physicochemical properties governing ovastacin–substrate interactions as well as the individual characteristics that distinguish ovastacin from similar proteases, such as meprins and tolloid. Eventually, we identified several substrates whose cleavage could affect mammalian fertilization. Consequently, these substrates indicate newly identified functions of ovastacin in mammalian fertilization beyond zona pellucida hardening. |
DDC: | 610 Medizin 610 Medical sciences |
Institution: | Johannes Gutenberg-Universität Mainz |
Department: | FB 04 Medizin |
Place: | Mainz |
ROR: | https://ror.org/023b0x485 |
DOI: | http://doi.org/10.25358/openscience-9911 |
Version: | Published version |
Publication type: | Zeitschriftenaufsatz |
License: | CC BY |
Information on rights of use: | https://creativecommons.org/licenses/by/4.0/ |
Journal: | The FEBS journal 291 1 |
Pages or article number: | 114 131 |
Publisher: | Wiley-Blackwell |
Publisher place: | Oxford u.a. |
Issue date: | 2024 |
ISSN: | 1742-464X |
Publisher DOI: | 10.1111/febs.16954 |
Appears in collections: | DFG-491381577-H |
Files in This Item:
File | Description | Size | Format | ||
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substrate_profiling_of_the_me-20240108094036064.pdf | 2.48 MB | Adobe PDF | View/Open |