The C-terminal domain of the MERS coronavirus M protein contains a trans-Golgi network localization signal.

Anabelle Perrier, Ariane Bonnin, Lowiese Desmarets, Adeline Danneels, Anne Goffard, Yves Rouillé, Jean Dubuisson, Sandrine Belouzard

The Journal of biological chemistry 2019 Sep 27

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Coronavirus M proteins represent the major protein component of the viral envelope. They play an essential role during viral assembly by interacting with all of the other structural proteins. Coronaviruses bud into the endoplasmic reticulum (ER)-Golgi intermediate compartment (ERGIC), but the mechanisms by which M proteins are transported from their site of synthesis, the ER, to the budding site remain poorly understood. Here, we investigated the intracellular trafficking of the Middle East respiratory syndrome coronavirus (MERS-CoV) M protein. Subcellular localization analyses revealed that the MERS-CoV M protein is retained intracellularly in the trans-Golgi network (TGN), and we identified two motifs in the distal part of the C-terminal domain as being important for this specific localization. We identified the first motif as a functional diacidic DxE ER export signal, because substituting Asp-211 and Glu-213 with alanine induced retention of the MERS-CoV M in the ER. The second motif, 199KxGxYR204, was responsible for retaining the M protein in the TGN. Substitution of this motif resulted in MERS-CoV M leakage toward the plasma membrane. We further confirmed the role of 199KxGxYR204 as a TGN retention signal by using chimeras between MERS-CoV M and the M protein of infectious bronchitis virus (IBV). Our results indicated that the C-terminal domains of both proteins determine their specific localization, namely TGN and ERGIC/cis-Golgi for MERS-M and IBV-M, respectively. Our findings indicate that MERS-CoV M protein localizes to the TGN because of the combined presence of an ER export signal and a TGN retention motif. © 2019 Perrier et al.

Citation

Anabelle Perrier, Ariane Bonnin, Lowiese Desmarets, Adeline Danneels, Anne Goffard, Yves Rouillé, Jean Dubuisson, Sandrine Belouzard. The C-terminal domain of the MERS coronavirus M protein contains a trans-Golgi network localization signal. The Journal of biological chemistry. 2019 Sep 27;294(39):14406-14421