Journal article

A mortise-tenon joint in the transmembrane domain modulates autotransporter assembly into bacterial outer membranes

Denisse L Leyton, Matthew D Johnson, Rajiv Thapa, Gerard HM Huysmans, Rhys A Dunstan, Nermin Celik, Hsin-Hui Shen, Dorothy Loo, Matthew J Belousoff, Anthony W Purcell, Ian R Henderson, Travis Beddoe, Jamie Rossjohn, Lisandra L Martin, Richard A Strugnell, Trevor Lithgow

Nature Communications | NATURE RESEARCH | Published : 2014

Abstract

Bacterial autotransporters comprise a 12-stranded membrane-embedded β-barrel domain, which must be folded in a process that entraps segments of an N-terminal passenger domain. This first stage of autotransporter folding determines whether subsequent translocation can deliver the N-terminal domain to its functional form on the bacterial cell surface. Here, paired glycine-aromatic 'mortise and tenon' motifs are shown to join neighbouring β-strands in the C-terminal barrel domain, and mutations within these motifs slow the rate and extent of passenger domain translocation to the surface of bacterial cells. In line with this, biophysical studies of the autotransporter Pet show that the conserved..

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Grants

Awarded by Australian Research Council (ARC)


Awarded by National Health and Medical Research Council


Awarded by EMBO-Pasteur Fellowship


Awarded by Biotechnology and Biological Sciences Research Council


Funding Acknowledgements

We thank Victoria Hewitt and Chris Stubenrauch for critical comments on the manuscript and Lillian Wong for technical assistance. We gratefully acknowledge the support of the Australian Research Council (ARC) for research funding through the ARC Super Science Fellowship grant FS110200015 (to T.L., J.R., R.A.S. and L.L.M.) and the National Health and Medical Research Council through a NHMRC Program Grant 606788 (to T.L. and R.A.S.). G.H.M.H. is a recipient of a Marie Curie Fellowship and an EMBO-Pasteur Fellowship (PIEF-GA-2010-272611; ALTF 1088-2010). M.J.B. is an NHMRC Postdoctoral Fellow, A.W.P. is an NHMRC Senior Research Fellow and J.R. an NHMRC Australia Fellow. D.L.L. and H.S. are ARC Super Science Fellows, T.L. is an ARC Australian Laureate Fellow.