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

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

Research output: Contribution to journalArticleResearchpeer-review

22 Citations (Scopus)

Abstract

Bacterial autotransporters comprise a 12-stranded membrane-embedded beta-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 beta-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 residues significantly quicken completion of the folding reaction and promote stability of the autotransporter barrel domain. Comparative genomics demonstrate conservation of glycine-aromatic residue pairings through evolution as a previously unrecognized feature of all autotransporter proteins.
Original languageEnglish
Pages (from-to)1 - 11
Number of pages11
JournalNature Communications
Volume5
Issue number(Art. No.: 4239)
DOIs
Publication statusPublished - 2014

Cite this

Leyton, Denisse L ; Johnson, Matthew D ; Thapa, Rajiv ; Huysmans, Gerard ; Dunstan, Rhys A ; Celik, Nermin ; Shen, Hsin-Hui ; Loo, Dorothy ; Belousoff, Matthew J ; Purcell, Anthony W ; Henderson, Ian R ; Beddoe, Travis C ; Rossjohn, Jamie ; Martin, Lisandra L ; Strugnell, Richard Anthony ; Lithgow, Trevor J. / A mortise-tenon joint in the transmembrane domain modulates autotransporter assembly into bacterial outer membranes. In: Nature Communications. 2014 ; Vol. 5, No. (Art. No.: 4239). pp. 1 - 11.
@article{f5bff75334124296b84e0363c150e242,
title = "A mortise-tenon joint in the transmembrane domain modulates autotransporter assembly into bacterial outer membranes",
abstract = "Bacterial autotransporters comprise a 12-stranded membrane-embedded beta-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 beta-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 residues significantly quicken completion of the folding reaction and promote stability of the autotransporter barrel domain. Comparative genomics demonstrate conservation of glycine-aromatic residue pairings through evolution as a previously unrecognized feature of all autotransporter proteins.",
author = "Leyton, {Denisse L} and Johnson, {Matthew D} and Rajiv Thapa and Gerard Huysmans and Dunstan, {Rhys A} and Nermin Celik and Hsin-Hui Shen and Dorothy Loo and Belousoff, {Matthew J} and Purcell, {Anthony W} and Henderson, {Ian R} and Beddoe, {Travis C} and Jamie Rossjohn and Martin, {Lisandra L} and Strugnell, {Richard Anthony} and Lithgow, {Trevor J}",
year = "2014",
doi = "10.1038/ncomms5239",
language = "English",
volume = "5",
pages = "1 -- 11",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "(Art. No.: 4239)",

}

A mortise-tenon joint in the transmembrane domain modulates autotransporter assembly into bacterial outer membranes. / Leyton, Denisse L; Johnson, Matthew D; Thapa, Rajiv; Huysmans, Gerard; Dunstan, Rhys A; Celik, Nermin; Shen, Hsin-Hui; Loo, Dorothy; Belousoff, Matthew J; Purcell, Anthony W; Henderson, Ian R; Beddoe, Travis C; Rossjohn, Jamie; Martin, Lisandra L; Strugnell, Richard Anthony; Lithgow, Trevor J.

In: Nature Communications, Vol. 5, No. (Art. No.: 4239), 2014, p. 1 - 11.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - A mortise-tenon joint in the transmembrane domain modulates autotransporter assembly into bacterial outer membranes

AU - Leyton, Denisse L

AU - Johnson, Matthew D

AU - Thapa, Rajiv

AU - Huysmans, Gerard

AU - Dunstan, Rhys A

AU - Celik, Nermin

AU - Shen, Hsin-Hui

AU - Loo, Dorothy

AU - Belousoff, Matthew J

AU - Purcell, Anthony W

AU - Henderson, Ian R

AU - Beddoe, Travis C

AU - Rossjohn, Jamie

AU - Martin, Lisandra L

AU - Strugnell, Richard Anthony

AU - Lithgow, Trevor J

PY - 2014

Y1 - 2014

N2 - Bacterial autotransporters comprise a 12-stranded membrane-embedded beta-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 beta-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 residues significantly quicken completion of the folding reaction and promote stability of the autotransporter barrel domain. Comparative genomics demonstrate conservation of glycine-aromatic residue pairings through evolution as a previously unrecognized feature of all autotransporter proteins.

AB - Bacterial autotransporters comprise a 12-stranded membrane-embedded beta-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 beta-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 residues significantly quicken completion of the folding reaction and promote stability of the autotransporter barrel domain. Comparative genomics demonstrate conservation of glycine-aromatic residue pairings through evolution as a previously unrecognized feature of all autotransporter proteins.

UR - http://www.nature.com/ncomms/2014/140626/ncomms5239/pdf/ncomms5239.pdf

U2 - 10.1038/ncomms5239

DO - 10.1038/ncomms5239

M3 - Article

VL - 5

SP - 1

EP - 11

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - (Art. No.: 4239)

ER -