A novel predicted ADP-ribosyltransferase-like family conserved in eukaryotic evolution

Author:

Wyżewski Zbigniew1,Gradowski Marcin2,Krysińska Marianna2,Dudkiewicz Małgorzata2,Pawłowski Krzysztof234

Affiliation:

1. Institute of Biological Sciences, Cardinal Stefan Wyszynski University in Warsaw, Warszawa, Poland

2. Department of Biochemistry and Microbiology, Warsaw University of Life Sciences - SGGW, Warszawa, Poland

3. Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX, United States

4. Department of Translational Medicine, Lund University, Lund, Sweden

Abstract

The presence of many completely uncharacterized proteins, even in well-studied organisms such as humans, seriously hampers full understanding of the functioning of the living cells. ADP-ribosylation is a common post-translational modification of proteins; also nucleic acids and small molecules can be modified by the covalent attachment of ADP-ribose. This modification, important in cellular signalling and infection processes, is usually executed by enzymes from the large superfamily of ADP-ribosyltransferases (ARTs). Here, using bioinformatics approaches, we identify a novel putative ADP-ribosyltransferase family, conserved in eukaryotic evolution, with a divergent active site. The hallmark of these proteins is the ART domain nestled between flanking leucine-rich repeat (LRR) domains. LRRs are typically involved in innate immune surveillance. The novel family appears as putative novel ADP-ribosylation-related actors, most likely pseudoenzymes. Sequence divergence and lack of clearly detectable “classical” ART active site suggests the novel domains are pseudoARTs, yet atypical ART activity, or alternative enzymatic activity cannot be excluded. We propose that this family, including its human member LRRC9, may be involved in an ancient defense mechanism, with analogies to the innate immune system, and coupling pathogen detection to ADP-ribosyltransfer or other signalling mechanisms.

Publisher

PeerJ

Subject

General Agricultural and Biological Sciences,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

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