Structures of Lysenin Reveal a Shared Evolutionary Origin for Pore-Forming Proteins And Its Mode of Sphingomyelin Recognition

Luigi De Colibus,Andreas F.-P Sonnen,Keith J Morris,C Alistair Siebert,Patrizia Abrusci,Jürgen Plitzko,Vesna Hodnik,Matthias Leippe,Emanuela Volpi,Gregor Anderluh,Robert J.C Gilbert

doi:10.1016/j.str.2012.06.011

Abstract

SummaryPore-forming proteins insert from solution into membranes to create lesions, undergoing a structural rearrangement often accompanied by oligomerization. Lysenin, a pore-forming toxin from the earthworm Eisenia fetida, specifically interacts with sphingomyelin (SM) and may confer innate immunity against parasites by attacking their membranes to form pores. SM has important roles in cell membranes and lysenin is a popular SM-labeling reagent. The structure of lysenin suggests common ancestry with other pore-forming proteins from a diverse set of eukaryotes and prokaryotes. The complex with SM shows the mode of its recognition by a protein in which both the phosphocholine headgroup and one acyl tail are specifically bound. Lipid interaction studies and assays using viable target cells confirm the functional reliance of lysenin on this form of SM recognition.

Highlights

Pore-forming proteins have evolved in all kingdoms of life, and are increasingly understood to exist in a limited number of superfamilies
Pore-forming proteins insert from solution into membranes to create lesions, undergoing a structural rearrangement often accompanied by oligomerization
The complex with SM shows the mode of its recognition by a protein in which both the phosphocholine headgroup and one acyl tail are bound

Summary

Introduction

Pore-forming proteins have evolved in all kingdoms of life, and are increasingly understood to exist in a limited number of superfamilies. The cholesterol-dependent cytolysins (CDCs) of Gram-positive bacteria, for instance, are structurally related to the membrane-attack complex/perforin (MACPF) family of proteins found in humans and Plasmodium (Amino et al, 2008; Anderluh and Lakey, 2008; Rosado et al, 2008). Another family is exemplified by aerolysin from Aeromonas hydrophila (Parker et al, 1994) and ε-toxin from Clostridium perfringens but includes the fungal Laetiporus sulphureus lytic lectin (LSL) (Anderluh and Lakey, 2008; Cole et al, 2004; Mancheno et al, 2005). We describe the structure of an additional member of the aerolysin family

Results

Discussion

Conclusion