Substrate Profiling of Mitochondrial Caseinolytic Protease P via a Site‐Specific Photocrosslinking Approach
Abstract: Approaches for profiling protease substrates are critical for defining protease functions, but remain challenging tasks. We combine genetic code expansion, photocrosslinking and proteomics to identify substrates of the mitochondrial (mt) human caseinolytic protease P (hClpP). Site‐specific incorporation of the diazirine‐bearing amino acid DiazK into the inner proteolytic chamber of hClpP, followed by UV‐irradiation of cells, allows to covalently trap substrate proteins of hClpP and to substantiate hClpP's major involvement in maintaining overall mt homeostasis. In addition to confirming many of the previously annotated hClpP substrates, our approach adds a diverse set of new proteins to the hClpP interactome. Importantly, our workflow allows identifying substrate dynamics upon application of external cues in an unbiased manner. Identification of unique hClpP‐substrate proteins upon induction of mt oxidative stress, suggests that hClpP counteracts oxidative stress by processing of proteins that are involved in respiratory chain complex synthesis and maturation as well as in catabolic pathways.
- Location
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Deutsche Nationalbibliothek Frankfurt am Main
- Extent
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Online-Ressource
- Language
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Englisch
- Bibliographic citation
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Substrate Profiling of Mitochondrial Caseinolytic Protease P via a Site‐Specific Photocrosslinking Approach ; day:14 ; month:01 ; year:2022 ; extent:1
Angewandte Chemie / International edition. International edition ; (14.01.2022) (gesamt 1)
- Creator
- DOI
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10.1002/anie.202111085
- URN
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urn:nbn:de:101:1-2022011514301036721509
- Rights
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Last update
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15.08.2025, 7:21 AM CEST
Data provider
Deutsche Nationalbibliothek. If you have any questions about the object, please contact the data provider.
Associated
- Nguyen, Tuan‐Anh
- Gronauer, Thomas F.
- Nast‐Kolb, Timon
- Sieber, Stephan A.
- Lang, Kathrin
Other Objects (12)
Substrate Profiling of Mitochondrial Caseinolytic Protease P via a Site‐Specific Photocrosslinking Approach
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Substrate Profiling of Mitochondrial Caseinolytic Protease P via a Site‐Specific Photocrosslinking Approach
Eine Photocrosslinker Sonde zur Erfassung der Substrate der caseinolytischen Protease P
A Photocrosslinking Probe to Capture the Substrates of Caseinolytic Protease P
Virulence Attenuation through Chemical and Genetic Manipulation of the Staphylococcus aureus ClpXP Protease
Structural and functional characterization of the ClpXP1/2 protease complex from Listeria monocytogenes
Profiling the Heme‐Binding Proteomes of Bacteria Using Chemical Proteomics
Three membered rings as probes in the activity based protein profiling
Design and application of natural product derived probes for activity based protein profiling
Target identification of natural products by activity based protein profiling and a whole proteome inventory of background photocrosslinker binding
Synthesis of gamma-lactones for activity based protein profiling: Investigation of their protein reactivity and inhibition of bacterial virulence
Functionalised Cofactor Mimics for Interactome Discovery and Beyond
Funktionalisierte Cofaktor‐Analoga für die Erforschung von Interaktomen und darüber hinaus
Substrate Profiling of Mitochondrial Caseinolytic Protease P via a Site‐Specific Photocrosslinking Approach
Eine Photocrosslinker Sonde zur Erfassung der Substrate der caseinolytischen Protease P
A Photocrosslinking Probe to Capture the Substrates of Caseinolytic Protease P
Virulence Attenuation through Chemical and Genetic Manipulation of the Staphylococcus aureus ClpXP Protease
Structural and functional characterization of the ClpXP1/2 protease complex from Listeria monocytogenes
Profiling the Heme‐Binding Proteomes of Bacteria Using Chemical Proteomics
Three membered rings as probes in the activity based protein profiling
Design and application of natural product derived probes for activity based protein profiling
Target identification of natural products by activity based protein profiling and a whole proteome inventory of background photocrosslinker binding
Synthesis of gamma-lactones for activity based protein profiling: Investigation of their protein reactivity and inhibition of bacterial virulence
Functionalised Cofactor Mimics for Interactome Discovery and Beyond