The Role of Ubiquitin-Proteasome System in the Pathogenesis of Severe Acute Respiratory Syndrome Coronavirus-2 Disease

Figure 1

Types of ubiquitination ligases and ligase E3 function. (a) The HECT type of E3 ligases contains the conserved C-terminal HECT domain, and the N-terminal consists of different domains depending on the specific subtype. HECT-type E3 ligases are involved in the ubiquitination process, which involves a two-step reaction: ubiquitin is first carried out by an E2 ligase binding to the HECT domain of the E3 ligase and then transferred to a catalytic cysteine on the E3 ligase; the second step is the transfer of ubiquitin from the E3 ligase to the substrate. (b) The RING type E3 ligases are characterized by the presence of a zinc-binding domain called a RING at the N-terminal. Ring E3s mediate a direct transfer of ubiquitin from E2 ligase to the substrate. (c) The U-box type E3 ligases contain a U-box domain at the C-terminal, which is responsible for binding the ubiquitin-charged E2 ligase and stimulating ubiquitin transfer. (d) The RBR type E3 ligases consist of two predicted RING domains (RING1 and RING2) separated by an IBR domain. RBR type E3 ligases’ catalyzed ubiquitination process involves a two-step reaction where ubiquitin is first transferred to a catalytic RING2 domain on the E3 and then to the substrate [24]. (a) HECT E3 ligase; (b) RING E3 ligase; (c) U-box E3 ligase; and (d) RBR E3 ligase.

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