Hermanns, Thomas, Woiwode, Ilka, Guerreiro, Ricardo F. M., Vogt, Robert, Lammers, Michael ORCID: 0000-0003-4168-4640 and Hofmann, Kay (2020). An evolutionary approach to systematic discovery of novel deubiquitinases, applied to Legionella. Life Sci. Alliance, 3 (9). COLD SPRING HARBOR: LIFE SCIENCE ALLIANCE LLC. ISSN 2575-1077

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Abstract

Deubiquitinating enzymes (DUBs) are important regulators of the posttranslational protein ubiquitination system. Mammalian genomes encode about 100 different DUBs, which can be grouped into seven different classes. Members of other DUB classes are found in pathogenic bacteria, which use them to target the host defense. By combining bioinformatical and experimental approaches, we address the question if the known DUB families have a common evolutionary ancestry and share conserved features that set them apart from other proteases. By systematically comparing family-specific hidden Markov models, we uncovered distant relationships between established DUBs and other cysteine protease families. Most DUB families share a conserved aromatic residue linked to the active site, which restricts the cleavage of substrates with side chains at the S2 position, corresponding to Gly-75 in ubiquitin. By applying these criteria to Legionella pneumophila ORFs, we identified lpg1621 and lpg1148 as deubiquitinases, characterized their cleavage specificities, and confirmed the importance of the aromatic gatekeeper motif for substrate selection.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Hermanns, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Woiwode, IlkaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Guerreiro, Ricardo F. M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vogt, RobertUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lammers, MichaelUNSPECIFIEDorcid.org/0000-0003-4168-4640UNSPECIFIED
Hofmann, KayUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-320782
DOI: 10.26508/lsa.202000838
Journal or Publication Title: Life Sci. Alliance
Volume: 3
Number: 9
Date: 2020
Publisher: LIFE SCIENCE ALLIANCE LLC
Place of Publication: COLD SPRING HARBOR
ISSN: 2575-1077
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
MOLECULAR-BASIS; ACTIVE-SITE; UBIQUITIN; SPECIFICITY; PROTEIN; CHEMISTRY; REVEALSMultiple languages
BiologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/32078

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