The cryo-EM structure of the acid activatable pore-forming immune effector Macrophage-expressed gene 1

Siew Siew Pang, Charles Bayly-Jones, Mazdak Radjainia, Bradley A. Spicer, Ruby H. P. Law, Adrian W. Hodel, Edward S. Parsons, Susan M. Ekkel, Paul J. Conroy, Georg Ramm, Hariprasad Venugopal, Phillip I. Bird, Bart W. Hoogenboom, Ilia Voskoboinik, Yann Gambin, Emma Sierecki, Michelle A. Dunstone () and James C. Whisstock ()
Additional contact information
Siew Siew Pang: Monash University
Charles Bayly-Jones: Monash University
Mazdak Radjainia: Monash University
Bradley A. Spicer: Monash University
Ruby H. P. Law: Monash University
Adrian W. Hodel: University College London
Edward S. Parsons: University College London
Susan M. Ekkel: Monash University
Paul J. Conroy: Monash University
Georg Ramm: Monash University
Hariprasad Venugopal: Monash University
Phillip I. Bird: Monash University
Bart W. Hoogenboom: University College London
Ilia Voskoboinik: Peter MacCallum Cancer Centre
Yann Gambin: University of New South Wales
Emma Sierecki: University of New South Wales
Michelle A. Dunstone: Monash University
James C. Whisstock: Monash University

Nature Communications, 2019, vol. 10, issue 1, 1-9

Abstract: Abstract Macrophage-expressed gene 1 (MPEG1/Perforin-2) is a perforin-like protein that functions within the phagolysosome to damage engulfed microbes. MPEG1 is thought to form pores in target membranes, however, its mode of action remains unknown. We use cryo-Electron Microscopy (cryo-EM) to determine the 2.4 Å structure of a hexadecameric assembly of MPEG1 that displays the expected features of a soluble prepore complex. We further discover that MPEG1 prepore-like assemblies can be induced to perforate membranes through acidification, such as would occur within maturing phagolysosomes. We next solve the 3.6 Å cryo-EM structure of MPEG1 in complex with liposomes. These data reveal that a multi-vesicular body of 12 kDa (MVB12)-associated β-prism (MABP) domain binds membranes such that the pore-forming machinery of MPEG1 is oriented away from the bound membrane. This unexpected mechanism of membrane interaction suggests that MPEG1 remains bound to the phagolysosome membrane while simultaneously forming pores in engulfed bacterial targets.

Date: 2019
References: Add references at CitEc
Citations: View citations in EconPapers (4)

Downloads: (external link)
https://www.nature.com/articles/s41467-019-12279-2 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-12279-2

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-019-12279-2

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().