Understanding how pore-forming proteins punch holes in membranes
Grant number: DP160101874 | Funding period: 2016 - 2020
This project aims to unravel missing molecular details of how a major superfamily of proteins is able to drill holes in cell membranes. Animals, plants, fungi and bacteria all use pore-forming proteins as cell-killing weapons of mass destruction. Despite their lethal nature and their roles in infection and immunity, how these proteins work remains enigmatic. Project outcomes could reveal novel mechanisms general to these essential proteins and provide fundamental insights in understanding vital physiological processes across all kingdoms of life. Ultimately, the knowledge gained may prove useful in the engineering of membrane pores as highly specific sensors for a variety of molecules with n..View full description
Related publications (8)
A Key Motif in the Cholesterol-Dependent Cytolysins Reveals a Large Family of Related Proteins
Jordan C Evans, Bronte A Johnstone, Sara L Lawrence, Craig J Morton, Michelle P Christie, Michael W Parker, Rodney K Tweten
The cholesterol-dependent cytolysins (CDCs) are bacterial, β-barrel, pore-forming toxins. A central enigma of the pore-forming mec..
Cholesterol-Dependent Cytolysins: Membrane and Protein Structural Requirements for Pore Formation
Craig J Morton, Marc-Antoine Sani, Michael W Parker, Frances Separovic
The cholesterol-dependent cytolysins (CDCs) are a family of bacterial protein toxins specifically targeting eukaryotic cells throu..
An Intermolecular pi-Stacking Interaction Drives Conformational Changes Necessary to beta-Barrel Formation in a Pore-Forming Toxin
Joshua R Burns, Craig J Morton, Michael W Parker, Rodney K Tweten
The crystal structures of the soluble monomers of the pore-forming cholesterol-dependent cytolysins (CDCs) contain two α-helical b..
The Structural Basis for a Transition State That Regulates Pore Formation in a Bacterial Toxin
Kristin R Wade, Sara L Lawrence, Allison J Farrand, Eileen M Hotze, Michael J Kuiper, Michael A Gorman, Michelle P Christie, Santosh Panjikar, Craig J Morton, Michael W Parker, Rodney K Tweten
The cholesterol-dependent cytolysin (CDC) genes are present in bacterial species that span terrestrial, vertebrate, and invertebra..
Cholesterol-dependent cytolysins: from water-soluble state to membrane pore.
Michelle P Christie, Bronte A Johnstone, Rodney K Tweten, Michael W Parker, Craig J Morton
The cholesterol-dependent cytolysins (CDCs) are a family of bacterial toxins that are important virulence factors for a number of ..
Structural Basis for Receptor Recognition by the Human CD59-Responsive Cholesterol-Dependent Cytolysins
Sara L Lawrence, Michael A Gorman, Susanne C Feil, Terrence D Mulhern, Michael J Kuiper, Adam J Ratner, Rodney K Tweten, Craig J Morton, Michael W Parker
Cholesterol-dependent cytolysins (CDCs) are a family of pore-forming toxins that punch holes in the outer membrane of eukaryotic c..