University of Surrey

Test tubes in the lab Research in the ATI Dance Research

Mycolactone reveals substrate-driven complexity of Sec61-dependent transmembrane protein biogenesis

McKenna, M, Simmonds, Rachel and High, S (2017) Mycolactone reveals substrate-driven complexity of Sec61-dependent transmembrane protein biogenesis Journal of Cell Science, 130. pp. 1307-1320.

[img]
Preview
Text
1307.full.pdf - Version of Record

Download (8MB) | Preview
[img]
Preview
Text (licence)
SRI_deposit_agreement.pdf
Available under License : See the attached licence file.

Download (33kB) | Preview
[img] Text
jcs.198655.full.pdf - Accepted version Manuscript
Restricted to Repository staff only
Available under License : See the attached licence file.

Download (4MB)

Abstract

Mycolactone is the exotoxin virulence factor produced by Mycobacterium ulcerans, the pathogen responsible for Buruli ulcer. The skin lesions and immunosuppression characteristic of this disease result from the action of mycolactone, which targets the Sec61 complex and inhibits the co-translational translocation of secretory proteins into the endoplasmic reticulum. In this study, we investigate the effect of mycolactone on the Sec61-dependent biogenesis of different classes of transmembrane protein (TMP). Our data suggest that the effect of mycolactone on TMP biogenesis depends on how the nascent chain initially engages the Sec61 complex. For example, translocation of TMP lumenal domains driven by an N-terminal, cleavable signal sequence is efficiently inhibited by mycolactone. In contrast, the effect of mycolactone on protein translocation driven solely by a non-cleavable signal anchor/transmembrane domain depends on which flanking region is translocated. For example, while translocation of the region N-terminal to a signal anchor/transmembrane domain is refractive to mycolactone, C-terminal translocation is efficiently inhibited. Our findings highlight the diversity of Sec61-dependent translocation and provide a molecular basis for understanding the effect of mycolactone on the biogenesis of different TMPs.

Item Type: Article
Subjects : Biosciences and Medicine
Divisions : Faculty of Health and Medical Sciences > School of Biosciences and Medicine
Authors :
NameEmailORCID
McKenna, MUNSPECIFIEDUNSPECIFIED
Simmonds, RachelRachel.Simmonds@surrey.ac.ukUNSPECIFIED
High, SUNSPECIFIEDUNSPECIFIED
Date : 1 September 2017
Funders : BBSRC
Identification Number : 10.1242/jcs.198655
Copyright Disclaimer : © 2017. Published by The Company of Biologists Ltd. http://creativecommons.org/licenses/by/3.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
Uncontrolled Keywords : Endoplasmic reticulum / Membrane protein / Mycobacterium ulcerans / Mycolactone / Protein translocation / Sec61
Related URLs :
Depositing User : Symplectic Elements
Date Deposited : 01 Mar 2017 15:19
Last Modified : 06 Jul 2017 06:56
URI: http://epubs.surrey.ac.uk/id/eprint/813657

Actions (login required)

View Item View Item

Downloads

Downloads per month over past year


Information about this web site

© The University of Surrey, Guildford, Surrey, GU2 7XH, United Kingdom.
+44 (0)1483 300800