The NMR solution structure of the ion channel peptaibol chrysospermin C bound to dodecylphosphocholine micelles

Abstract

Chrysospermin C is a 19-residue peptaibol capable of forming transmembrane ion channels in phospholipid bilayers. The conformation of chrysospermin C bound to dodecylphosphocholine micelles has been solved using heteronuclear NMR spectroscopy. Selective 15N-labeling and 13C-labeling of specific alpha-aminoisobutyric acid residues was used to obtain complete stereospecific assignments for all eight alpha-aminoisobutyric acid residues. Structures were calculated using 339 distance constraints and 40 angle constraints obtained from NMR data. The NMR structures superimpose with mean global rmsd values to the mean structure of 0. 27 A (backbone heavy atoms) and 0.42 A (all heavy atoms). Chrysospermin C bound to decylphosphocholine micelles displays two well-defined helices at the N-terminus (residues Phe1-Aib9) and C-terminus (Aib13-Trp-ol19). A slight bend preceding Pro14, i.e. encompassing residues 10-12, results in an angle of approximately 38 degrees between the mean axes of the two helical regions. The bend structure observed for chrysospermin C is compatible with the sequences of all 18 long peptaibols and may represent a common 'active' conformation. The structure of chrysospermin C shows clear hydrophobic and hydrophilic surfaces which would be appropriate for the formation of oligomeric ion channels.

Molecular modeling of the reductase domain to elucidate the reaction mechanism of reduction of peptidyl thioester into its corresponding alcohol in non-ribosomal peptide synthetases

“…The reductase substrates included linear peptides such as alamethicin (1AMT), antiamoebin I (1GQ0), trichotoxin (1M24), chryospermin C (1EE7) and gramicidin (1NRM) [36-39]. The above substrates are ≈18-20 amino acids long and linear.…”

The structure and behavior of the NA-CATH antimicrobial peptide with liposomes

“…Within its class of α-helical AMPs, the NA-CATH helix is relatively straight (Fig. 3A(II)), in contrast to curved helical structures [81][82][83][84] and even helices separated by a helical turn [85]. For example, LL-37, a single helical cathelicidin AMP, shows considerable curvature (Fig.…”

“…The hydrophobic residues are distributed along the opposite surface. The last nine C-terminal amino acids are predominantly hydrophobic and unstructured, in contrast to similar α-helical AMPs [81][82][83][84][85]. The few lysine and arginine residues of LL-37 (PDB: 2K6O, [84]) are located not only on the convex surface, but also on the outer edges of the helix (Fig.…”

“…With stable pore formation, one would expect a pattern of shielded residues, embedded in the bilayer, which is inconsistent with our NMR findings. Curved helical AMP conformations, unlike the NA-CATH NMR solution, have a propensity for pore formation [81,86] or are predicted to do so based on their structure [26,82]. According to Lad et al [24] and Gazit et al [87], the helix-break/bend-helix structures allow for the flexibility required to penetrate the bilayer.…”

Antiamoebin I in Methanol Solution: Rapid Exchange between Right‐Handed and Left‐Handed 310‐Helical Conformations

“…The data for chrysospermin C in DPC micelles solution [43], harzianin HC-IX in MeOH solution [24], pseudokonins KL in MeOH solution [51], and Zrv-IIB in MeOH solution [29] were analyzed (for all of these peptides: i) right-handed helical conformation, ii) absence of conformational dynamics associated with changes in helix handedness, and iii) complete stereospecific assignment of Aib Me groups, were reported). The N-or C-terminal Aib residues were excluded from the analysis due to possible enhanced mobility.…”