PDBsum entry 2mcu

Antimicrobial protein

PDB id: 2mcu

Contents

Protein chain

23 a.a.

PDB id:

2mcu

Name:

Antimicrobial protein

Title:

Solid-state nmr structure of piscidin 1 in aligned 3:1 phosphatidylcholine/phosphoglycerol lipid bilayers

Structure:

Moronecidin. Chain: a. Synonym: piscidin-1. Engineered: yes

Source:

Synthetic: yes. Morone saxatilis. Striped bass. Organism_taxid: 34816. Other_details: synthetic construct

NMR struc:

10 models

Authors:

R.Fu,Y.Tian,B.S.Perrin Jr.,C.V.Grant,R.W.Pastor,M.L.Cotten

Key ref:

B.S.Perrin et al. (2014). 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. PubMed id: 24410116 DOI: 10.1021/ja411119m

Date:

27-Aug-13 Release date: 22-Jan-14

Protein chain

Q8UUG0  (MORO_MORSA) -  Moronecidin from Morone saxatilis

Seq: 79 a.a.

Struc: 23 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

DOI no: 10.1021/ja411119m

J Am Chem Soc 136:3491-3504 (2014)

PubMed id: 24410116

High-resolution structures and orientations of antimicrobial peptides piscidin 1 and piscidin 3 in fluid bilayers reveal tilting, kinking, and bilayer immersion.

B.S.Perrin, Y.Tian, R.Fu, C.V.Grant, E.Y.Chekmenev, W.E.Wieczorek, A.E.Dao, R.M.Hayden, C.M.Burzynski, R.M.Venable, M.Sharma, S.J.Opella, R.W.Pastor, M.L.Cotten.

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.