A lysine-methionine exchange in a coronavirus surface protein transforms a retention motif into an endocytosis signal

作者：Paul Andre; Trincone Anna; Siewert Sandra; Herrler Georg; Schwegmann Wessels Christel^*

来源：Biological Chemistry, 2014, 395(6): 657-665.

DOI：10.1515/hsz-2013-0282

• protein sorting
• protein transport
• TGEV S protein
• tyrosine-based sorting signal
• VSV G protein

Transmissible gastroenteritis virus (TGEV) is an enveloped (+) RNA virus belonging to the family Coronaviridae. Among the viral membrane proteins, the spike (S) protein mediates receptor recognition/attachment to the host cell and fusion of viral and cellular membranes. The cytoplasmic tail of the S protein contains a tyrosine-dependent sorting signal with the consensus sequence YXX Phi. In the context of the S protein of TGEV (1440YEPI1443), this motif acts as a retention signal, preventing surface expression of the protein. Here, we show that a chimeric S protein, containing the six C-terminal amino acids of the glycoprotein G of vesicular stomatitis virus (VSV) is no longer retained intracellularly, despite the presence of the tyrosine tetrapeptide motif. Following transport to the cell surface, the chimeric protein was rapidly endocytosed. Analysis of mutant proteins generated by site-directed mutagenesis revealed that a single amino acid exchange (1445K/M, position: +2 downstream of the tyrosine-based motif) was responsible for the altered sorting behavior.

• 出版日期2014-6