Real-time visualization of perforin nanopore assembly

Carl Leung, Adrian W. Hodel, Amelia J. Brennan, Natalya Lukoyanova, Sharon Tran, Colin M. House, Stephanie C. Kondos, James C. Whisstock, Michelle A. Dunstone, Joseph A. Trapani, Ilia Voskoboinik, Helen R. Saibil, Bart W. Hoogenboom

Research output: Contribution to journalArticleResearchpeer-review

37 Citations (Scopus)


Perforin is a key protein of the vertebrate immune system. Secreted by cytotoxic lymphocytes as soluble monomers, perforin can self-assemble into oligomeric pores of 10–20 nm inner diameter in the membranes of virus-infected and cancerous cells. These large pores facilitate the entry of pro-apoptopic granzymes, thereby rapidly killing the target cell. To elucidate the pathways of perforin pore assembly, we carried out real-time atomic force microscopy and electron microscopy studies. Our experiments reveal that the pore assembly proceeds via a membrane-bound prepore intermediate state, typically consisting of up to approximately eight loosely but irreversibly assembled monomeric subunits. These short oligomers convert to more closely packed membrane nanopore assemblies, which can subsequently recruit additional prepore oligomers to grow the pore size.

Original languageEnglish
Pages (from-to)467-473
Number of pages9
JournalNature Nanotechnology
Publication statusPublished - May 2017


  • applications of AFM
  • nanopores

Cite this