PE5-PPE4-EspG3 heterotrimer structure from mycobacterial ESX-3 secretion system gives insight into cognate substrate recognition by ESX systems.

The Journal of Biological Chemistry
Zachary A WilliamsonKonstantin V Korotkov

Abstract

Mycobacterium tuberculosis has evolved numerous type VII secretion (ESX) systems to secrete multiple factors important for both growth and virulence across their cell envelope. ESX-1, ESX-3, and ESX-5 systems have been shown to each secrete a distinct set of substrates, including PE and PPE families of proteins, named for conserved Pro-Glu and Pro-Pro-Glu motifs in their N termini. Proper secretion of the PE-PPE proteins requires the presence of EspG, with each system encoding its own unique copy. There is no cross-talk between any of the ESX systems, and how each EspG recognizes its subset of PE-PPE proteins is currently unknown. The only current structural characterization of PE-PPE-EspG heterotrimers is from the ESX-5 system. Here we present the crystal structure of the PE5mt-PPE4mt-EspG3mm heterotrimer from the ESX-3 system. Our heterotrimer reveals that EspG3mm interacts exclusively with PPE4mt in a similar manner to EspG5, shielding the hydrophobic tip of PPE4mt from solvent. The C-terminal helical domain of EspG3mm is dynamic, alternating between "open" and "closed" forms, and this movement is likely functionally relevant in the unloading of PE-PPE heterodimers at the secretion machinery. In contrast to the previously so...Continue Reading

References

Dec 20, 1993·Journal of Molecular Biology·M C Lawrence, P M Colman
May 24, 2001·Biophysical Journal·D I SvergunM H Koch
Dec 2, 2004·Acta Crystallographica. Section D, Biological Crystallography·Paul Emsley, Kevin Cowtan
Apr 12, 2007·Proceedings of the National Academy of Sciences of the United States of America·Jürgen BoschWim G J Hol
Apr 17, 2007·Microbiological Research·Janka TeutschbeinThomas Munder
Aug 8, 2007·Journal of Molecular Biology·Evgeny Krissinel, Kim Henrick
Oct 9, 2007·Nature Reviews. Microbiology·Abdallah M AbdallahWilbert Bitter
Aug 1, 2007·Journal of Applied Crystallography·Airlie J McCoyRandy J Read
Oct 31, 2009·PLoS Pathogens·Wilbert BitterRoland Brosch
Feb 4, 2010·Acta Crystallographica. Section D, Biological Crystallography·Wolfgang Kabsch
Feb 4, 2010·Acta Crystallographica. Section D, Biological Crystallography·Paul D AdamsPeter H Zwart
May 26, 2012·Science·P Andrew Karplus, Kay Diederichs
Jun 27, 2012·Proceedings of the National Academy of Sciences of the United States of America·Maria H DalekeWilbert Bitter
Jul 31, 2012·The Journal of Biological Chemistry·Maria H DalekeEdith N G Houben
Jul 4, 2013·Journal of Structural Biology·Konstantin V KorotkovWim G J Hol
Apr 23, 2014·Nucleic Acids Research·Xavier Robert, Patrice Gouet
Oct 3, 2014·Proceedings of the National Academy of Sciences of the United States of America·Damian C Ekiert, Jeffery S Cox
Jun 9, 2015·Journal of Structural Biology·Natalia KorotkovaKonstantin V Korotkov
Sep 27, 2016·Nature Reviews. Microbiology·Matthias I GröschelRoland Brosch
Apr 11, 2017·Nature Microbiology·Katherine S H BeckhamEdith N G Houben
Jul 16, 2017·Protein Science : a Publication of the Protein Society·Thomas D GoddardThomas E Ferrin
Aug 25, 2017·Protein Science : a Publication of the Protein Society·Elizabeth JurrusNathan A Baker
Aug 27, 2017·The Journal of Biological Chemistry·Xin ChenShannon Wing-Ngor Au
Oct 27, 2017·Protein Science : a Publication of the Protein Society·Christopher J WilliamsDavid C Richardson
Nov 9, 2017·Advances in Experimental Medicine and Biology·Giovanni DeloguRiccardo Manganelli
Nov 13, 2018·Journal of Molecular Biology·Anne T TuukkanenKonstantin V Korotkov
Apr 13, 2019·Nucleic Acids Research·Fábio MadeiraRodrigo Lopez
Jul 3, 2019·Bioinformatics·Liisa Holm
Oct 10, 2019·Nature·Nikolaos FamelisSebastian Geibel
Oct 14, 2019·Protein Science : a Publication of the Protein Society·Liisa Holm
Dec 31, 2019·ELife·Nicole PoweleitOren S Rosenberg

❮ Previous
Next ❯

Citations

May 28, 2021·Nature Reviews. Microbiology·Angel Rivera-CalzadaSebastian Geibel
Aug 3, 2021·Current Research in Structural Biology·Abril GijsbersRaimond B G Ravelli

❮ Previous
Next ❯

Related Concepts

Related Feeds

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.