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1.C.33.1.9
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).

Accession Number:P32194
Protein Name:Protegrin-1
Length:149
Molecular Weight:16677.00
Species:Sus scrofa (Pig) [9823]
Number of TMSs:1
Location1 / Topology2 / Orientation3: Secreted1
Substrate anions

Cross database links:

RefSeq: NP_001116621.1   
Entrez Gene ID: 100144483   
Pfam: PF00666   
KEGG: ssc:100144483   

Gene Ontology

GO:0005576 C:extracellular region
GO:0042742 P:defense response to bacterium

References (6)

[1] “Identification of a new member of the protegrin family by cDNA cloning.”  Zhao C.et.al.   8013647
[2] “The structure of porcine protegrin genes.”  Zhao C.et.al.   7628604
[3] “Protegrins: leukocyte antimicrobial peptides that combine features of corticostatic defensins and tachyplesins.”  Kokryakov V.N.et.al.   8335113
[4] “Primary structure of three cationic peptides from porcine neutrophils. Sequence determination by the combined usage of electrospray ionization mass spectrometry and Edman degradation.”  Mirgorodskaya O.A.et.al.   8375505
[5] “Synthesis and solution structure of the antimicrobial peptide protegrin-1.”  Aumelase A.et.al.   8647100
[6] “Solution structure of protegrin-1, a broad-spectrum antimicrobial peptide from porcine leukocytes.”  Fahrner R.L.et.al.   8807886
Structure:
1PG1   1ZY6     

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FASTA formatted sequence
1:	METQRASLCL GRWSLWLLLL ALVVPSASAQ ALSYREAVLR AVDRLNEQSS EANLYRLLEL 
61:	DQPPKADEDP GTPKPVSFTV KETVCPRPTR QPPELCDFKE NGRVKQCVGT VTLDQIKDPL 
121:	DITCNEVQGV RGGRLCYCRR RFCVCVGRG