SARS-CoV-2 targets PDZ proteins in cell-cell junction

PSD95/Dlg1/ZO-1 (PDZ) domains are protein-protein recognition sequences, consisting of 80–90 amino acids that bind to a PDZ-binding motif (PBM), usually located at the end of the carboxy-terminus of a target protein (Hung AY & Sheng M 2002; Gerek ZN et al. 2009; Munz M et al. 2012). Proteins containing PDZ domains are typically found in the cell cytoplasm or in association with the plasma membrane and play a role in a variety of cellular processes such as cell-cell junctions, cellular polarity, and signal transduction pathways. The multidomain structure of PDZ-containing proteins enables them to interact with multiple binding partners simultaneously, thereby assembling larger protein complexes (Harris BZ & Lim WA 2001). Viruses also encode PBM-containing proteins that bind to cellular PDZ proteins. Viral PBMs target cellular PDZ-containing proteins involved in tight junction formation, cell polarity establishment, and apoptosis (Javier RT & Rice AP 2011).

PSD95/Dlg1/ZO-1（PDZ）结构域为蛋白质-蛋白质识别序列，由80至90个氨基酸组成，能够与PDZ结合基序（PBM）结合，通常位于目标蛋白羧基末端的区域（Hung AY & Sheng M 2002；Gerek ZN et al. 2009；Munz M et al. 2012）。含有PDZ结构域的蛋白质通常存在于细胞质中或与质膜相结合，并在多种细胞过程中发挥作用，如细胞间连接、细胞极性和信号转导途径。PDZ结构域所含蛋白质的多结构域结构使它们能够同时与多个结合伙伴相互作用，从而组装成更大的蛋白质复合体（Harris BZ & Lim WA 2001）。病毒亦编码含有PBM的蛋白质，这些蛋白质能够与细胞PDZ蛋白质结合。病毒PBM靶向参与紧密连接形成、细胞极性建立和细胞凋亡的细胞PDZ结构域所含蛋白质（Javier RT & Rice AP 2011）。