Structure of the Cathelicidin Motif of Protegrin-3 Precursor Jean-Frédéric Sanchez, François Hoh, Marie-Paule Strub, André Aumelas, Christian Dumas  Structure  Volume 10, Issue 10, Pages 1363-1370 (October 2002) DOI: 10.1016/S0969-2126(02)00859-6

Figure 1 Structure-Based Sequences Alignment of Representative Members of the Cathelicidin Family Antimicrobial Proteins (Top) Sequence alignment of their cathelicidin motif with location of secondary structures in ProS and sequence variability of 42 cathelicidin sequences [2]. Arrows show the limits of exons deduced from the cathelicidin genes organization [3]. Disulfide bonds are displayed. (Bottom) Sequences of the corresponding antibacterial peptides coded by the fourth exon [3]. The numbering of the protegrin corresponds to that of the holoprotein. Abbreviations: ProS is for protegrin 1-5 precursors; pr39_pig is for antibacterial protein pr_39 precursor; bct1_caphi and bct5_bovin are for bactenecin-1 and 5 precursors, respectively; cp18 is for antimicrobial protein cap18 precursor; fa39_human is for antibacterial protein fall-39 precursor; cram-mouse is for cathelicidin-related antimicrobial peptide precursor. Structure 2002 10, 1363-1370DOI: (10.1016/S0969-2126(02)00859-6)

Figure 2 Ribbon Diagram of the ProS Structure (A) Ribbon representation showing the N-terminal α-helix (α1, L32-Q48), the antiparallel four-stranded β sheet: β1(N53-L60), β2 (K74-P86), β3 (V104-V111), β4 (D121-E126). The disordered loops (Q62-P70 and Q115-D118) are represented here as dotted lines. The two disulfide bridges (C85-C96 and C107-C124) are also shown (sulfur atoms in yellow). (B) Same representation as (A) but rotated by 90°. The figures have been computed using Molscript [39] and Raster3D [40]. Structure 2002 10, 1363-1370DOI: (10.1016/S0969-2126(02)00859-6)

Figure 3 The Overall Fold of the Swapped ProS Dimer and the Hinge Region (A) View of the σA1-weighted 2Fo − Fc electron density map around the hinge region (61–70 residues). The red and blue arrows represent the β1 and β2 strands of chains A and B, respectively. (B) Ribbon model of the swapped domains of dimeric ProS (red and blue chains). The disulfide bridges C85-C96 and C107-C124 are displayed (yellow sulfur atoms). The two monomers are related by a vertical crystallographic 2-fold axis. (C) Detailed stereo view of the hinge region stabilized by packing in the crystal. The interacting residues are shown as ball-and-stick models and colored in yellow for the hinge segment (chain A), in green for the β2 strand (chain B) and gray for the neighbor molecule. Two H-bonds are formed between backbone atoms of chain A (K65 and D67 residues) and that of the neighbor molecule (F98 and E100 residues). For clarity, side chains of some residues are not displayed. Structure 2002 10, 1363-1370DOI: (10.1016/S0969-2126(02)00859-6)

Figure 4 Views of the Model for Interaction of ProS with PG1 (A) Ribbon model of ProS-PG1 holoprotein. The PG1 peptide docked to the core of ProS is displayed in green and contributes to the extension of the β sheet. The loop containing the elastase cleavage site is shown in red. (B) An other view showing the wrapping of the α helix by the six-stranded β sheet. The three disulfide bridges (sulfur atoms colored in yellow) contribute to the hydrophobic core at the interface between ProS and PG1. (C) The electrostatic potential on the molecular surface of ProS monomeric protein. Blue and red surface areas represent regions of positive and negative potentials, respectively, at 10 kT level. The C-terminal segment corresponding to the peptide is displayed as a green ribbon, with Arg side chains as sticks. Sulfur atoms are colored in yellow. The elastase cleavage site is shown by the arrow. The Figure 4C was prepared with GRASP [41]. Structure 2002 10, 1363-1370DOI: (10.1016/S0969-2126(02)00859-6)

Figure 5 Scheme Summarizing the Processing of Cathelicidin Antimicrobial Peptides and Their Currently Admitted Mechanisms of Membrane Permeation and Bacterial Lysis [4] Structure 2002 10, 1363-1370DOI: (10.1016/S0969-2126(02)00859-6)