PMID- 26654785 OWN - NLM STAT- MEDLINE DCOM- 20160907 LR - 20161126 IS - 0006-3002 (Print) IS - 0006-3002 (Linking) VI - 1858 IP - 3 DP - 2016 Mar TI - Protein-lipid interactions and non-lamellar lipidic structures in membrane pore formation and membrane fusion. PG - 487-99 LID - S0005-2736(15)00402-2 [pii] LID - 10.1016/j.bbamem.2015.11.026 [doi] AB - Pore-forming proteins and peptides act on their targeted lipid bilayer membranes to increase permeability. This approach to the modulation of biological function is relevant to a great number of living processes, including; infection, parasitism, immunity, apoptosis, development and neurodegeneration. While some pore-forming proteins/peptides assemble into rings of subunits to generate discrete, well-defined pore-forming structures, an increasing number is recognised to form pores via mechanisms which co-opt membrane lipids themselves. Among these, membrane attack complex-perforin/cholesterol-dependent cytolysin (MACPF/CDC) family proteins, Bax/colicin family proteins and actinoporins are especially prominent and among the mechanisms believed to apply are the formation of non-lamellar (semi-toroidal or toroidal) lipidic structures. In this review I focus on the ways in which lipids contribute to pore formation and contrast this with the ways in which lipids are co-opted also in membrane fusion and fission events. A variety of mechanisms for pore formation that involve lipids exists, but they consistently result in stable hybrid proteolipidic structures. These structures are stabilised by mechanisms in which pore-forming proteins modify the innate capacity of lipid membranes to respond to their environment, changing shape and/or phase and binding individual lipid molecules directly. In contrast, and despite the diversity in fusion protein types, mechanisms for membrane fusion are rather similar to each other, mapping out a pathway from pairs of separated compartments to fully confluent fused membranes. Fusion proteins generate metastable structures along the way which, like long-lived proteolipidic pore-forming complexes, rely on the basic physical properties of lipid bilayers. Membrane fission involves similar intermediates, in the reverse order. I conclude by considering the possibility that at least some pore-forming and fusion proteins are evolutionarily related homologues. This article is part of a Special Issue entitled: Pore-Forming Toxins edited by Mauro Dalla Serra and Franco Gambale. CI - Copyright (c) 2015 Elsevier B.V. All rights reserved. FAU - Gilbert, Robert J C AU - Gilbert RJ AD - Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK. Electronic address: gilbert@strubi.ox.ac.uk. LA - eng GR - 090532/Z/09/Z/Wellcome Trust/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20151202 PL - Netherlands TA - Biochim Biophys Acta JT - Biochimica et biophysica acta JID - 0217513 RN - 0 (Colicins) RN - 0 (Membrane Lipids) RN - 0 (bcl-2-Associated X Protein) RN - 126465-35-8 (Perforin) SB - IM MH - Animals MH - *Cell Membrane/chemistry/metabolism MH - *Colicins/chemistry/metabolism MH - Humans MH - *Membrane Fusion MH - *Membrane Lipids/chemistry/metabolism MH - *Perforin/chemistry/metabolism MH - *bcl-2-Associated X Protein/chemistry/metabolism OTO - NOTNLM OT - Membrane fission OT - Membrane fusion OT - Membrane pore formation OT - Molecular evolution OT - Non-lamellar (toroidal) lipids EDAT- 2015/12/15 06:00 MHDA- 2016/09/08 06:00 CRDT- 2015/12/15 06:00 PHST- 2015/08/15 00:00 [received] PHST- 2015/10/23 00:00 [revised] PHST- 2015/11/30 00:00 [accepted] PHST- 2015/12/15 06:00 [entrez] PHST- 2015/12/15 06:00 [pubmed] PHST- 2016/09/08 06:00 [medline] AID - S0005-2736(15)00402-2 [pii] AID - 10.1016/j.bbamem.2015.11.026 [doi] PST - ppublish SO - Biochim Biophys Acta. 2016 Mar;1858(3):487-99. doi: 10.1016/j.bbamem.2015.11.026. Epub 2015 Dec 2.