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Effects of MACPF/CDC proteins on lipid membranes

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Abstract

Recent work on the MACPF/CDC superfamily of pore-forming proteins has focused on the structural analysis of monomers and pore-forming oligomeric complexes. We set the family of proteins in context and highlight aspects of their function which the direct and exclusive equation of oligomers with pores fails to explain. Starting with a description of the distribution of MACPF/CDC proteins across the domains of life, we proceed to show how their evolutionary relationships can be understood on the basis of their structural homology and re-evaluate models for pore formation by perforin, in particular. We furthermore highlight data showing the role of incomplete oligomeric rings (arcs) in pore formation and how this can explain small pores generated by oligomers of proteins belonging to the family. We set this in the context of cell biological and biophysical data on the proteins’ function and discuss how this helps in the development of an understanding of how they act in processes such as apicomplexan parasites gliding through cells and exiting from cells.

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Abbreviations

ALY:

Anthrolysin

Bth:

Bacillus thetaiotaomicron MACPF protein

CDCs:

Cholesterol-dependent cytolysins

CTL:

Cytotoxic T lymphocytes

EM:

Electron microscopy

GrB:

Granzyme B

ILY:

Intermedilysin

LLO:

Listeriolysin

MACPF:

Membrane attack complex/perforin

MAC:

Membrane attack complex

PFN:

Perforin

PFO:

Perfringolysin

PLY:

Pneumolysin

PLPs:

Perforin-like proteins

Plu:

Photorhabdus luminescens MACPF protein

PPLPs:

Plasmodium perforin-like proteins

PV:

Parasitophorous vacuole

SLO:

Streptolysin

TMH:

Trans-membrane hairpin (present in the soluble forms of CDC/MACPFs as α-helices)

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Acknowledgments

We would like to thank Tilen Praper for the work performed with planar lipid bilayers and Robert Liddington and Alexander Aleshin for discussion and for providing the model of the complement membrane attack complex. R.J.C.G. is a Royal Society University Research Fellow and the Oxford Division of Structural Biology is part of the Wellcome Trust Centre for Human Genetics, Wellcome Trust Core Award Grant Number 090532/Z/09/Z.M.D.S. would like to thank the Nanosmart project from the Provincia Autonoma di Trento for support. G. A. would like to thank the Slovenian Research Agency for support.

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Authors and Affiliations

  1. Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford, OX3 7BN, UK

    Robert J. C. Gilbert

  2. Department of Biology, Biotechnical Faculty, University of Ljubljana, Večna pot 111, 1000, Ljubljana, Slovenia

    Miha Mikelj & Gregor Anderluh

  3. National Research Council, Institute of Biophysics and Bruno Kessler Foundation, via alla Cascata 56/C, 38123, Trento, Italy

    Mauro Dalla Serra

  4. Department of Medicine, NorthShore University HealthSystem Research Institute, Evanston, IL, 60201, USA

    Christopher J. Froelich

  5. National Institute of Chemistry, Hajdrihova 19, 1000, Ljubljana, Slovenia

    Gregor Anderluh

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  1. Robert J. C. Gilbert
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  3. Mauro Dalla Serra
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Correspondence to Robert J. C. Gilbert or Gregor Anderluh.

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Gilbert, R.J.C., Mikelj, M., Dalla Serra, M. et al. Effects of MACPF/CDC proteins on lipid membranes. Cell. Mol. Life Sci. 70, 2083–2098 (2013). https://doi.org/10.1007/s00018-012-1153-8

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  • DOI: https://doi.org/10.1007/s00018-012-1153-8

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