title: Oligomerization of the antimicrobial peptide Protegrin-5 in a membrane-mimicking environment. Structural studies by high-resolution NMR spectroscopy.
abstract: Protegrin pore formation is believed to occur in a stepwise fashion that begins with a nonspecific peptide interaction with the negatively charged bacterial cell walls via hydrophobic and positively charged amphipathic surfaces. There are five known nature protegrins (PG1-PG5), and early studies of PG-1 (PDB ID:1PG1) shown that it could form antiparallel dimer in membrane mimicking environment which could be a first step for further oligomeric membrane pore formation. Later, we solved PG-2 (PDB ID:2MUH) and PG-3 (PDB ID:2MZ6) structures in the same environment and for PG-3 observed a strong dααNOE effects between residues R18 and F12, V14, and V16. These "inconsistent" with monomer structure NOEs appears due to formation of an additional antiparallel β-sheet between two monomers. It was also suggested that there is a possible association of protegrins dimers to form octameric or decameric β-barrels in an oligomer state. In order to investigate a more detailed oligomerization process of protegrins, in the present article we report the monomer (PDB ID: 2NC7) and octamer pore structures of the protegrin-5 (PG-5) in the presence of DPC micelles studied by solution NMR spectroscopy. In contrast to PG-1, PG-2, and PG-3 studies, for PG-5 we observed not only dimer NOEs but also several additional NOEs between side chains, which allows us to calculate an octamer pore structure of PG-5 that was in good agreement with previous AFM and PMF data.
authors: Kazan Federal University, 18 Kremlevskaya St., 420008, Kazan, Russian Federation.
authors: Konstantin S
authors: KS
authors: Usachev
authors: Kazan Federal University, 18 Kremlevskaya St., 420008, Kazan, Russian Federation.
authors: Olga A
authors: OA
authors: Kolosova
authors: Kazan Federal University, 18 Kremlevskaya St., 420008, Kazan, Russian Federation.
authors: Evelina A
authors: EA
authors: Klochkova
authors: Kazan Federal University, 18 Kremlevskaya St., 420008, Kazan, Russian Federation.
authors: Aidar R
authors: AR
authors: Yulmetov
authors: Kazan Federal University, 18 Kremlevskaya St., 420008, Kazan, Russian Federation.
authors: Albert V
authors: AV
authors: Aganov
authors: Kazan Federal University, 18 Kremlevskaya St., 420008, Kazan, Russian Federation. vladimir.klochkov@kpfu.ru.
authors: Vladimir V
authors: VV
authors: Klochkov
mesh_terms: D000595:Amino Acid Sequence; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry*; D002462:Cell Membrane / Q000737:chemistry; D057927:Hydrophobic and Hydrophilic Interactions; D009682:Magnetic Resonance Spectroscopy; D008567:Membranes, Artificial; D008823:Micelles; D008958:Models, Molecular; D000072757:Protein Conformation, beta-Strand; D055503:Protein Multimerization
chemical_list: D023181:Antimicrobial Cationic Peptides; D008567:Membranes, Artificial; D008823:Micelles; C094882:protegrin-5
keywords: Antibiotic; Antimicrobial peptide; NMR; Pore; Protegrin; Structure