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Supramolecular Structure of Self‐Assembling Alamethicin Analog Studied by ESR and PELDOR
Author(s) -
Milov Alexander D.,
Samoilova Marina I.,
Tsvetkov Yuri D.,
Jost Micha,
Peggion Cristina,
Formaggio Fernando,
Crisma Marco,
Toniolo Claudio,
Handgraaf JanWillem,
Raap Jan
Publication year - 2007
Publication title -
chemistry and biodiversity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.427
H-Index - 70
eISSN - 1612-1880
pISSN - 1612-1872
DOI - 10.1002/cbdv.200790110
Subject(s) - alamethicin , chemistry , supramolecular chemistry , electron paramagnetic resonance , rotational diffusion , spin label , molecule , rotational correlation time , dipole , crystallography , resonance (particle physics) , nuclear magnetic resonance , membrane , bilayer , organic chemistry , biochemistry , physics , particle physics
Three analogs of alamethicin F50/5, labelled with the TOAC (=‘2,2,6,6‐tetramethylpiperidin‐1‐oxyl‐4‐amino‐4‐carboxylic acid’) spin label at positions 1 ( Alm1 ), 8 ( Alm8 ), and 16 ( Alm16 ), resp., were studied by Electron‐Spin‐Resonance (ESR) and Pulsed Electron–Electron Double‐Resonance (PELDOR) techniques in solvents of different polarity to investigate the self‐assembly of amphipathic helical peptides in membrane‐mimicking environments. In polar solvents, alamethicin forms homogeneous solutions. In the weakly polar chloroform/toluene 1 : 1 mixture, however, this peptide forms aggregates that are detectable at 293 K by ESR in liquid solution, as well as by PELDOR in frozen, glassy solution at 77 K. In liquid solution, free alamethicin molecules and their aggregates show rotational‐mobility correlation times τ r of 0.87 and 5.9 ns, resp. Based on these values and analysis of dipole–dipole interactions of the TOAC labels in the aggregates, as determined by PELDOR, the average number N of alamethicin molecules in the aggregates is estimated to be less than nine. A distance‐distribution function between spin labels in the supramolecular aggregate was obtained. This function exhibits two maxima: a broad one at a distance of 3.0 nm, and a wide one at a distance of ca. 7 nm. A molecular‐dynamics (MD)‐based model of the aggregate, consisting of two parallel tetramers, each composed of four molecules arranged in a ‘head‐to‐tail’ fashion, is proposed, accounting for the observed distances and their distribution.