Shi, X. , Botting, C. H., Li, P. , Niglas, M., Brennan, B. , Shirran, S. L., Szemiel, A. M. and Elliott, R. M. (2016) Bunyamwera orthobunyavirus glycoprotein precursor Is processed by cellular signal peptidase and signal peptide peptidase. Proceedings of the National Academy of Sciences of the United States of America, 113(31), pp. 8825-8830. (doi: 10.1073/pnas.1603364113) (PMID:27439867) (PMCID:PMC4978261)
|
Text
120245.pdf - Accepted Version 12MB |
Abstract
The M genome segment of Bunyamwera virus (BUNV)—the prototype of both the Bunyaviridae family and the Orthobunyavirus genus—encodes the glycoprotein precursor (GPC) that is proteolytically cleaved to yield two viral structural glycoproteins, Gn and Gc, and a nonstructural protein, NSm. The cleavage mechanism of orthobunyavirus GPCs and the host proteases involved have not been clarified. In this study, we investigated the processing of BUNV GPC and found that both NSm and Gc proteins were cleaved at their own internal signal peptides (SPs), in which NSm domain I functions as SPNSm and NSm domain V as SPGc. Moreover, the domain I was further processed by a host intramembrane-cleaving protease, signal peptide peptidase, and is required for cell fusion activities. Meanwhile, the NSm domain V (SPGc) remains integral to NSm, rendering the NSm topology as a two-membrane-spanning integral membrane protein. We defined the cleavage sites and boundaries between the processed proteins as follows: Gn, from residue 17–312 or nearby residues; NSm, 332–477; and Gc, 478–1433. Our data clarified the mechanism of the precursor cleavage process, which is important for our understanding of viral glycoprotein biogenesis in the genus Orthobunyavirus and thus presents a useful target for intervention strategies.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Elliott, Professor Richard and Szemiel, Dr Agnieszka and Brennan, Dr Benjamin and Shi, Dr Xiaohong and Li, Dr Ping |
| Authors: | Shi, X., Botting, C. H., Li, P., Niglas, M., Brennan, B., Shirran, S. L., Szemiel, A. M., and Elliott, R. M. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research |
| Journal Name: | Proceedings of the National Academy of Sciences of the United States of America |
| Publisher: | National Academy of Sciences |
| ISSN: | 0027-8424 |
| ISSN (Online): | 1091-6490 |
| Published Online: | 20 July 2016 |
| Copyright Holders: | Copyright © 2016 National Academy of Sciences |
| First Published: | First published in Proceedings of the National Academy of Sciences of the United States of America 113(31): 8825-8830 |
| Publisher Policy: | Reproduced in accordance with the copyright policy of the publisher |
University Staff: Request a correction | Enlighten Editors: Update this record
Funder and Project Information
Funder and Project Information