muP2 prepore UM (107.37 MB)

Animation of the Perforin-2 (MPEG1) pre-pore which forms at neutral pH and likely precedes the acid-dependent transition to the bactericidal pore in phagosomes.

Download (107.37 MB)
posted on 03.07.2020, 16:39 by George Munson
Animation of the murine Perforin-2 (MPEG1) pre-pore. Perforin-2 is constitutively expressed in macrophages and other phagocytes. It plays an essential role in the destruction of microbes by permeabilizing the envelope of phagocytosed bacteria. This animations was rendered from PDB 6SB3 with UCSF Chimera ( Movies were captured with macOS Catalina applications Screenshot and Quicktime.

Supports Publication: Ni, T., Jiao, F., Yu, X., Aden, S., Ginger, L., Williams, S. I., Bai, F., Pražák, V., Karia, D., Stansfeld, P., Zhang, P., Munson, G., Anderluh, G., Scheuring, S., & Gilbert, R. J. C. (2020). Structure and mechanism of bactericidal mammalian perforin-2, an ancient agent of innate immunity. Science Advances, 6(5), eaax8286.

Publication Abstract:
Perforin-2 (MPEG1) is thought to enable the killing of invading microbes engulfed by macrophages and other phagocytes, forming pores in their membranes. Loss of perforin-2 renders individual phagocytes and whole organisms significantly more susceptible to bacterial pathogens. Here, we reveal the mechanism of perforin-2 activation and activity using atomic structures of pre-pore and pore assemblies, high-speed atomic force microscopy, and functional assays. Perforin-2 forms a pre-pore assembly in which its pore-forming domain points in the opposite direction to its membrane-targeting domain. Acidification then triggers pore formation, via a 180° conformational change. This novel and unexpected mechanism prevents premature bactericidal attack and may have played a key role in the evolution of all perforin family proteins.


Killing of intracellular bacteria by Perforin-2

National Institute of Allergy and Infectious Diseases

Find out more...


Select an IC:

  • AI - National Institute of Allergy and Infectious Diseases (NIAID)

Is this associated with a publication?


DOI(s) of associated publication(s):

I confirm there is no human identifiable information in this dataset.