1887

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Volume 91, Issue 6

A novel transmembrane domain mediating retention of a highly motile herpesvirus glycoprotein in the endoplasmic reticulum Free

Abstract

Gene of murine cytomegalovirus belongs to the large group of ‘private’ genes that show no homology to those of other cytomegalovirus species and are thought to represent ‘host adaptation’ genes involved in virus–host interaction. Previous interest in the gene product was based on the presence of an immunodominant CD8 T-cell epitope presented at the surface of infected cells, despite interference by viral immune-evasion proteins. Here, we provide data to reveal that the gene product shows unusual features in its cell biology. A novel strategy of mass-spectrometric analysis was employed to map the N terminus of the mature protein, 107 aa downstream of the start site of the predicted open reading frame. The resulting 36.5 kDa gene product is identified here as an integral type-I membrane glycoprotein with exceptional intracellular trafficking dynamics, moving within the endoplasmic reticulum (ER) and outer nuclear membrane with an outstandingly high lateral membrane motility, actually 100 times higher than those published for cellular ER-resident proteins. Notably, gp36.5/m164 does not contain any typical ER-retention/retrieval signals, such as the C-terminal motifs KKXX or KXKXX, and does not pass the Golgi apparatus. Instead, it belongs to the rare group of viral glycoproteins in which the transmembrane domain (TMD) itself mediates direct ER retention. This is the first report relating TMD usage of an ER-resident transmembrane protein to its lateral membrane motility as a paradigm in cell biology. We propose that TMD usage for ER retention facilitates free and fast floating in ER-related membranes and between ER subdomains.

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2010-06-01
2024-04-19
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A novel transmembrane domain mediating retention of a highly motile herpesvirus glycoprotein in the endoplasmic reticulum
J. Gen. Virol. 91, 1524 (2010); https://doi.org/10.1099/vir.0.018580-0
/content/journal/jgv/10.1099/vir.0.018580-0
/content/journal/jgv/10.1099/vir.0.018580-0
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Primers for cloning and mutagenesis [ PDF] (74 KB)

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Bioinformatics and mass-spectrometric analysis identifying the N terminus of the mature m164 protein [ PDF] (222 KB)

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