PreProtegrin-2 (prophenin-2; PF-2; PR-2). Exerts antimicrobial activity more effectively against Gram-negative bacteria than Gram-positive bacteria. The high resolution NMR structure has been solved (Usachev et al. 2015).  Its antimicrobial activities have been defined (Yasin et al. 1996, Miyasaki et al. 1997, Miyasaki et al. 1998, Cho et al. 1998).  The cooperativity exhibited by the activities of this and other antimicrobial peptides has been explained as a non-linear concentration dependence characterized by a threshold and a rapid rise to saturation as the concentration exceeds the threshold (Huang 2006).

Mammals

preProtegrin 2 of Sus scrofa

The LL-37 (LL37) peptide (cathelicidin) selectively permeabilizes the membranes of apoptotic human leukocytes, leaving viable cells unaffected (Björstad et al., 2009). It forms transmembrane pores (Lee et al., 2011).  It is derived by proteolysis from the cathelin (FALL-39) precursor in granulocytes (Gudmundsson et al. 1996; Li et al. 2016). LL-37 interacts with lipids and shows the formation of oligomers generating fibril-like supramolecular structures on membranes before it assembles into transmembrane pores expressing a modification of the toroidal pore model (Zeth and Sancho-Vaello 2017). Stable transmembrane pore formation occurs at 2.0-10.0 mμM (Lozeau et al. 2018). LL-37 interacts with lipids and forms oligomers generating fibril-like supramolecular structures on membranes before assembling into transmembrane pores with a deviation of the toroidal pore model (Zeth and Sancho-Vaello 2017). Peptides, indolicidin, aurein 1.2, magainin II, cecropin A and LL-37 all cause a general acceleration of essential lipid transport processes without altering the overall structure of the lipid membranes or creating organized pore-like structures (Nielsen et al. 2020). Rapid scrambling of the lipid composition associated with enhanced lipid transport may trigger lethal signaling processes and enhance ion transport. Cardiolipin prevents membrane-pore formation by magainin and the human cathelicidin LL-37 in phosphatidyl glycerol membranes, and this constitutes a plausible mechanism used by bacteria such as Staphylococcus aureus to act against stress perturbations and, thereby, gain resistance to antimicrobial agents (Rocha-Roa et al. 2021).

Animals

LL-37 peptide precursor of Homo sapiens (P49913)

Antimicrobial and antitumor cathelicidin 6 or BMAP27 of 158 aas and 1 or 2 TMSs. The structure and dynamics have been examined (Sahoo and Fujiwara 2016).

Cathelicidin 6 of Bos taurus (Bovine)

Cathelicidin antimicrobial peptide CATH4 precursor of 172 aas and 3 or 4 TMSs, 1 or 2 near the N-terminus and 2 near the C-terminus. CATH4-type peptides alter the diffusion modes of individual lipids during the membrane-specific action of As-CATH4 peptides (Wu et al. 2023).

CATH4 of Alligator sinensis

PreIndolicidin (pre-Cathelicidin-4) may function by a carrier mechanism to selectively transport anions (Rokitskaya et al., 2011).  The pig (ovine) homologue (SMAP29) is the source from which ovispirin, novispirin and novicidin, which may form torroidal pores, are derived (Sawai et al. 2002). Peptides, indolicidin, aurein 1.2, magainin II, cecropin A and LL-37 all cause a general acceleration of essential lipid transport processes without altering the overall structure of the lipid membranes or creating organized pore-like structures (Nielsen et al. 2020). Rapid scrambling of the lipid composition associated with enhanced lipid transport may trigger lethal signaling processes and enhance ion transport.

Mammals

PreIndolicidin of Bos taurus

Animals

 Cathelicidin-B1 of Gallus gallus (Q5F378)

Pro-protegrin-1 (PG-1) (149aas;1 N-terminal TMS) produced by porcine leukocytes. It forms an anion-selective β-sheet toroidal channel of 8 β-hairpins in a consecutive NCCN packing organization, yielding both parallel and antiparallel β-sheets (Jang et al., 2008; Capone et al., 2010). The 3-d structure is known. 97% identical to protegrin-2 (1.C.33.1.1).  A model of the protein in Gram-negative bacterial membranes has been proposed (Bolintineanu et al. 2012).  Protegrin peptides form octameric pores, and about 100 pores are sufficient to kill E. coli (Bolintineanu et al. 2010). The membrane-bound structure, lipid interactions, and dynamics of the arginine-rich beta-hairpin antimicrobial peptide PG-1 as studied by solid-state NMR are described by Tang and Hong 2009.  Protegrin stabilizes partial lipid-forming pores (Prieto et al. 2014).  A model of the protegrin-1 pore has been presented, suggesting that permeability of water through a single PG-1 pore is sufficient to cause fast cell death by osmotic lysis (Langham et al. 2008). Possibly, toroidal pore formation is driven by guanidinium-phosphate complexation, where the cationic Arg residues drag the anionic phosphate groups along as they insert into the hydrophobic part of the membrane (Tang et al. 2007).  Protegrin-1 is an 18-residue beta-hairpin antimicrobial peptide (AMP) that forms transmembrane beta-barrels in biological membranes. All-atom molecular dynamics simulations of various protegrin-1 oligomers on the membrane surface and in transmembrane topologies indicated that protegrin dimers are stable, whereas trimers and tetramers break down (Lipkin et al. 2017). Tetrameric arcs remained stably inserted in lipid membranes, but the pore water was displaced by lipid molecules. Unsheared protegrin beta-barrels opened into beta-sheets that surrounded stable aqueous pores, whereas tilted barrels with sheared hydrogen bonding patterns were stable in most topologies. A third type of pore consisted of multiple small oligomers surrounding a small, partially lipidic pore. Tachyplesin (TC# 1.C.34.1.1) showed less of a tendency to oligomerize than protegrin: the octameric bundle resulted in small pores surrounded by six peptides as monomers and dimers, with some peptides returning to the membrane surface. Theus, multiple configurations of protegrin oligomers may produce aqueous pores (Lipkin et al. 2017). PG-1 can insert into membranes provided that the external electric potential is large enough to first induce a water column or a pore within the lipid bilayer membrane. The highly charged PG-1 is capable, by itself, of inducing molecular electroporation (Lai and Kaznessis 2018).

Animals

Protegrin-1 of Sus scrofa (P32194)