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Membrane Transport Processes Analyzed by a Highly Parallel Nanopore Chip System at Single Protein Resolution
Published on: August 16, 2016
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Real-time visualization of perforin nanopore assembly.
Carl Leung1,2, Adrian W Hodel1,3, Amelia J Brennan4
1London Centre for Nanotechnology, University College London, London WC1H 0AH, UK.
Nature Nanotechnology
|February 7, 2017
Summary
Perforin monomers self-assemble into membrane pores to kill target cells. This study reveals a two-step pore assembly process involving a prepore intermediate, crucial for immune system function.
Area of Science:
- Immunology
- Cell Biology
- Biophysics
Background:
- Perforin is a critical protein in the vertebrate immune system.
- Cytotoxic lymphocytes secrete perforin monomers that form pores in target cell membranes.
- These pores enable granzyme entry, leading to rapid cell death.
Purpose of the Study:
- To elucidate the pathways of perforin pore assembly.
- To understand the intermediate states during pore formation.
Main Methods:
- Real-time atomic force microscopy (AFM).
- Electron microscopy (EM).
Main Results:
- Perforin pore assembly proceeds via a membrane-bound prepore intermediate.
- This intermediate typically consists of up to eight loosely assembled monomeric subunits.
- Prepore oligomers convert to closely packed nanopore assemblies and can grow in size.
Conclusions:
- The findings detail a novel two-step mechanism for perforin pore formation.
- Understanding this pathway is key to comprehending cytotoxic lymphocyte function.
- This research provides insights into the biophysical mechanisms of immune surveillance.
