Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.
FEBS Lett. 2021 Jul;595(13):1758-1767. doi: 10.1002/1873-3468.14109. Epub 2021 May 26.
The SARS-CoV-2 spike glycoprotein (spike) mediates viral entry by binding ACE2 receptors on host cell surfaces. Spike glycan processing and cleavage, which occur in the Golgi network, are important for fusion at the plasma membrane, promoting both virion infectivity and cell-to-cell viral spreading. We show that a KxHxx motif in the cytosolic tail of spike weakly binds the COPβ' subunit of COPI coatomer, which facilitates some recycling of spike within the Golgi, while releasing the remainder to the cell surface. Although histidine (KxHxx) has been proposed to be equivalent to lysine within di-lysine endoplasmic reticulum (ER) retrieval sequences, we show that histidine-to-lysine substitution (KxKxx) retains spike at the ER and prevents glycan processing, protease cleavage, and transport to the plasma membrane.
SARS-CoV-2 刺突糖蛋白（Spike）通过与宿主细胞表面的 ACE2 受体结合来介导病毒进入。糖基化处理和切割发生在高尔基网络中，对于质膜融合很重要，可促进病毒粒子的感染力和细胞间病毒的传播。我们发现，Spike 胞质尾部的 KxHxx 基序弱结合 COPI 衣被蛋白复合物的 COPβ'亚基，这有助于 Spike 在高尔基体内的部分回收，同时将其余部分释放到细胞膜表面。尽管有人提出组氨酸（KxHxx）在双赖氨酸内质网（ER）回收序列中相当于赖氨酸，但我们发现组氨酸到赖氨酸的替换（KxKxx）使 Spike 保留在 ER 中，并阻止糖基化处理、蛋白酶切割以及向质膜的运输。
