4WDC

High-resolution crystal structure of water-soluble FraC (mutation F16P)

Summary for 4WDC

• Entry DOI: 10.2210/pdb4wdc/pdb
• Descriptor: Fragaceatoxin C (2 entities in total)
• Functional Keywords: pore forming toxin, protein-lipid interaction, actinoporin, lipid packing, cholesterol, toxin
• Biological source: Actinia fragacea (Strawberry anemone)
• Total number of polymer chains: 1
• Total formula weight: 19696.24

Authors

Caaveiro, J.M.M.,Morante, K.,Tsumoto, K. (deposition date: 2014-09-08, release date: 2015-03-18, Last modification date: 2024-03-20)

Primary citation

Morante, K.,Caaveiro, J.M.,Tanaka, K.,Gonzalez-Manas, J.M.,Tsumoto, K.
A Pore-Forming Toxin Requires a Specific Residue for Its Activity in Membranes with Particular Physicochemical Properties
J.Biol.Chem., 290:10850-10861, 2015

PubMed Abstract: The physicochemical landscape of the bilayer modulates membrane protein function. Actinoporins are a family of potent hemolytic proteins from sea anemones acting at the membrane level. This family of cytolysins preferentially binds to target membranes containing sphingomyelin, where they form lytic pores giving rise to cell death. Although the cytolytic activity of the actinoporin fragaceatoxin C (FraC) is sensitive to vesicles made of various lipid compositions, it is far from clear how this toxin adjusts its mechanism of action to a broad range of physiochemical landscapes. Herein, we show that the conserved residue Phe-16 of FraC is critical for pore formation in cholesterol-rich membranes such as those of red blood cells. The interaction of a panel of muteins of Phe-16 with model membranes composed of raft-like lipid domains is inactivated in cholesterol-rich membranes but not in cholesterol-depleted membranes. These results indicate that actinoporins recognize different membrane environments, resulting in a wider repertoire of susceptible target membranes (and preys) for sea anemones. In addition, this study has unveiled promising candidates for the development of protein-based biosensors highly sensitive to the concentration of cholesterol within the membrane.

PubMed: 25759390
DOI: 10.1074/jbc.M114.615211

Experimental method

X-RAY DIFFRACTION (1.29 Å)