Abstract
Toxoplasma gondii (T. gondii) is an important human and veterinary pathogen causing life-threatening disease in immunocompromised patients. The UBL-UBA shuttle protein family are important components of the ubiquitin–proteasome system. Here, we identified a novel UBL-UBA shuttle protein DSK2b that is charactered by an N-terminal ubiquitin-like domain (UBL) and a C-terminal ubiquitin-associated domain (UBA). DSK2b was localized in the cytoplasm and nucleus. The deletion of dsk2b did not affect the degradation of ubiquitinated proteins, parasite growth in vitro or virulence in mice. The double-gene knockout of dsk2b and its paralogs dsk2a (ΔΔdsk2adsk2b) results in a significant accumulation of ubiquitinated proteins and the asynchronous division of T. gondii. The growth of ΔΔdsk2adsk2b was significantly inhibited in vitro, while virulence in mice was not attenuated. In addition, autophagy occurred in the ΔΔdsk2adsk2b, which was speculated to degrade the accumulated ubiquitinated proteins in the parasites. Overall, DSK2b is a novel UBL-UBA shuttle protein contributing to the degradation of ubiquitinated proteins and is important for the synchronous cell division of T. gondii.
Highlights
Toxoplasma gondii is a common veterinary and human pathogen that typically lives as an obligate intracellular parasite within host cells [1]
A UBL-UBA shuttle protein is charactered by a N-terminal ubiquitin-like domain (UBL) and a C-terminal ubiquitin-associated domain (UBA)
Further research based upon the SMART database showed that four of the thirteen proteins contain a UBL domain and a UBA domain (Figure 1a), including DDI1, RAD23, DSK2 and TGME49_240700
Summary
Toxoplasma gondii is a common veterinary and human pathogen that typically lives as an obligate intracellular parasite within host cells [1]. The host infected by T. gondii is usually asymptomatic; the parasite is life-threatening in immunocompromised individuals. Its fast growth is responsible for the pathology that develops in toxoplasmosis patients [2]. Ubiquitination is an important post-translational modification that regulates many cellular processes such as protein trafficking, protein localization, cellular signaling and transcription [3]. The most important function of ubiquitination is to mediate protein degradation by the proteasome, which is named the ubiquitin–proteasome system (UPS) [4]. 80–90% of ubiquitinated proteins are degraded by the UPS in a eukaryotic cell [5]
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