title: Lipid-protein nanodiscs offer new perspectives for structural and functional studies of water-soluble membrane-active peptides.
abstract: Lipid-protein nanodiscs (LPNs) are nanoscaled fragments of a lipid bilayer stabilized in solution by the apolipoprotein or a special membrane scaffold protein (MSP). In this work, the applicability of LPN-based membrane mimetics in the investigation of water-soluble membrane-active peptides was studied. It was shown that a pore-forming antimicrobial peptide arenicin-2 from marine lugworm (charge of +6) disintegrates LPNs containing both zwitterionic phosphatidylcholine (PC) and anionic phosphatidylglycerol (PG) lipids. In contrast, the spider toxin VSTx1 (charge of +3), a modifier of Kv channel gating, effectively binds to the LPNs containing anionic lipids (POPC/DOPG, 3 : 1) and does not cause their disruption. VSTx1 has a lower affinity to LPNs containing zwitterionic lipids (POPC), and it weakly interacts with the protein component of nanodiscs, MSP (charge of -6). The neurotoxin II (NTII, charge of +4) from cobra venom, an inhibitor of the nicotinic acetylcholine receptor, shows a comparatively low affinity to LPNs containing anionic lipids (POPC/DOPG, 3 : 1 or POPC/DOPS, 4 : 1), and it does not bind to LPNs/POPC. The obtained data show that NTII interacts with the LPN/POPC/DOPS surface in several orientations, and that the exchange process among complexes with different topologies proceeds fast on the NMR timescale. Only one of the possible NTII orientations allows for the previously proposed specific interaction between the toxin and the polar head group of phosphatidylserine from the receptor environment (Lesovoy et al., Biophys. J. 2009. V. 97. № 7. P. 2089-2097). These results indicate that LPNs can be used in structural and functional studies of water-soluble membrane-active peptides (probably except pore-forming ones) and in studies of the molecular mechanisms of peptide-membrane interaction.
authors.affiliation: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya Str., 16/10, 117997, Moscow, Russia.
authors.forename: Z O
authors.initials: ZO
authors.lastname: Shenkarev
authors.affiliation: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya Str., 16/10, 117997, Moscow, Russia.
authors.forename: E N
authors.initials: EN
authors.lastname: Lyukmanova
authors.affiliation: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya Str., 16/10, 117997, Moscow, Russia.
authors.forename: A S
authors.initials: AS
authors.lastname: Paramonov
authors.affiliation: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya Str., 16/10, 117997, Moscow, Russia.
authors.forename: P V
authors.initials: PV
authors.lastname: Panteleev
authors.affiliation: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya Str., 16/10, 117997, Moscow, Russia.
authors.forename: S V
authors.initials: SV
authors.lastname: Balandin
authors.affiliation: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya Str., 16/10, 117997, Moscow, Russia ; Lomonosov Moscow State University, GSP-1, Leninskie Gory, 1, Bldg. 12, 119991, Moscow, Russia.
authors.forename: M A
authors.initials: MA
authors.lastname: Shulepko
authors.affiliation: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya Str., 16/10, 117997, Moscow, Russia.
authors.forename: K S
authors.initials: KS
authors.lastname: Mineev
authors.affiliation: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya Str., 16/10, 117997, Moscow, Russia ; Moscow Institute of Physics and Technology (State University), Institutskii Pereulok, 9, 141700, Dolgoprudny, Moscow Region, Russia.
authors.forename: T V
authors.initials: TV
authors.lastname: Ovchinnikova
authors.affiliation: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya Str., 16/10, 117997, Moscow, Russia ; Lomonosov Moscow State University, GSP-1, Leninskie Gory, 1, Bldg. 12, 119991, Moscow, Russia.
authors.forename: M P
authors.initials: MP
authors.lastname: Kirpichnikov
authors.affiliation: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya Str., 16/10, 117997, Moscow, Russia ; Moscow Institute of Physics and Technology (State University), Institutskii Pereulok, 9, 141700, Dolgoprudny, Moscow Region, Russia.
authors.forename: A S
authors.initials: AS
authors.lastname: Arseniev
keywords: NMR spectroscopy; antimicrobial peptides; high-density lipoprotein particles; lipid-protein nanodiscs; membrane mimetics; membrane-active peptides; neurotoxins
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