2MCX

Solid-state NMR structure of piscidin 3 in aligned 1:1 phosphatidylethanolamine/phosphoglycerol lipid bilayers

Summary for 2MCX

• Entry DOI: 10.2210/pdb2mcx/pdb
• Related: 2JOS 2MCU 2MCV 2MCX 2OJM
• NMR Information: BMRB: 19457
• Descriptor: Piscidin-3 (1 entity in total)
• Functional Keywords: antimicrobial peptide, cationic, amphipathic, histidine rich, helical, lipid bilayers, bacterial cell membrane mimic, antimicrobial protein
• Biological source: Morone chrysops x Morone saxatilis (White bass x Striped bass)
• Cellular location: Secreted: P0C006
• Total number of polymer chains: 1
• Total formula weight: 2495.95

Authors

Fu, R.,Tian, Y.,Perrin Jr., B.S.,Grant, C.V.,Wieczorek, W.E.,Pastor, R.W.,Cotten, M.L. (deposition date: 2013-08-27, release date: 2014-01-22, Last modification date: 2024-10-30)

Primary citation

Perrin, B.S.,Tian, Y.,Fu, R.,Grant, C.V.,Chekmenev, E.Y.,Wieczorek, W.E.,Dao, A.E.,Hayden, R.M.,Burzynski, C.M.,Venable, R.M.,Sharma, M.,Opella, S.J.,Pastor, R.W.,Cotten, M.L.
High-resolution structures and orientations of antimicrobial peptides piscidin 1 and piscidin 3 in fluid bilayers reveal tilting, kinking, and bilayer immersion.
J.Am.Chem.Soc., 136:3491-3504, 2014

PubMed Abstract: While antimicrobial peptides (AMPs) have been widely investigated as potential therapeutics, high-resolution structures obtained under biologically relevant conditions are lacking. Here, the high-resolution structures of the homologous 22-residue long AMPs piscidin 1 (p1) and piscidin 3 (p3) are determined in fluid-phase 3:1 phosphatidylcholine/phosphatidylglycerol (PC/PG) and 1:1 phosphatidylethanolamine/phosphatidylglycerol (PE/PG) bilayers to identify molecular features important for membrane destabilization in bacterial cell membrane mimics. Structural refinement of (1)H-(15)N dipolar couplings and (15)N chemical shifts measured by oriented sample solid-state NMR and all-atom molecular dynamics (MD) simulations provide structural and orientational information of high precision and accuracy about these interfacially bound α-helical peptides. The tilt of the helical axis, τ, is between 83° and 93° with respect to the bilayer normal for all systems and analysis methods. The average azimuthal rotation, ρ, is 235°, which results in burial of hydrophobic residues in the bilayer. The refined NMR and MD structures reveal a slight kink at G13 that delineates two helical segments characterized by a small difference in their τ angles (<10°) and significant difference in their ρ angles (~25°). Remarkably, the kink, at the end of a G(X)4G motif highly conserved among members of the piscidin family, allows p1 and p3 to adopt ρ angles that maximize their hydrophobic moments. Two structural features differentiate the more potent p1 from p3: p1 has a larger ρ angle and less N-terminal fraying. The peptides have comparable depths of insertion in PC/PG, but p3 is 1.2 Å more deeply inserted than p1 in PE/PG. In contrast to the ideal α-helical structures typically assumed in mechanistic models of AMPs, p1 and p3 adopt disrupted α-helical backbones that correct for differences in the amphipathicity of their N- and C-ends, and their centers of mass lie ~1.2-3.6 Å below the plane defined by the C2 atoms of the lipid acyl chains.

PubMed: 24410116
DOI: 10.1021/ja411119m

Experimental method

SOLID-STATE NMR