Protegrin
| Identifiers | |
|---|---|
| Symbol | N/A |
| OPM superfamily | 226 |
| OPM protein | 1pg1 |
Protegrins are small peptides containing 16-18 amino acid residues. Protegrins were first discovered in porcine leukocytes and were found to have antimicrobial activity against bacteria, fungi, and some enveloped viruses.[1] The amino acid composition of protegrins contains six positively charged arginine residues and four cysteine residues.[2] Their secondary structure is classified as cysteine-rich β-sheet antimicrobial peptides, AMPs, that display limited sequence similarity to certain defensins and tachyplesins. In solution, the peptides fold to form an anti-parallel β-strand with the structure stabilized by two cysteine bridges formed among the four cysteine residues.[3] Recent studies suggest that protegrins can bind to lipopolysaccharide, a property that may help them to insert into the membranes of gram-negative bacteria and permeabilize them.[4]
Structure
There are five known porcine protegrins, PG-1 to PG-5.[5] Three were identified biochemically and rest of them were deduced from DNA sequences.[6]
The protegrins are synthesized from quadiripartite genes as 147 to 149 amino acid precursursors with a cathelin-like propiece.[5][7] Protegrin sequence is similar to certain prodefensins and tachyplesins, antibiotic peptides derived from the horseshoe crab.[1] Protegrin-1 that consists of 18 amino acids, six of which are arginine residues, forms two antiparallel β-sheets with a β-turn. Protegrin-2 is missing two carboxy terminal amino acids. So, Protegrin-2 is shorter than Protegrin-1 and it has one less positive charge. Protegrin-3 substitutes a glycine for an arginine at position 4 and it also has one less positive charge. Protegrin-4 substitutes a phenylalanine for a valine at position 14 and sequences are different in the β-turn. This difference makes protegrin-4 less polar than others and less positively charged. Protegrin-5 substitutes a proline for an arginine with one less positive charge.[5]
Mechanism of Action
Protegrin-1 induces membrane disruption by forming a pore/channel that leads to cell death.[8][9] This ability depends on its secondary structure.[10] It forms an oligomeric structure in the membrane that creates a pore. Two ways of the self association of protegrin-1 into a dimeric β-sheet, an antiparallel β-sheet with a turn-next-totail association or a parallel β-sheet with a turn-next-toturn association,[11] were suggested. The activity can be restored by stabilizing the peptide structure with the two disulfide bonds.[12] The interacts with membranes depends on membrane lipid composition[13] and the cationic nature of the protegrin-1 adapts to the amphipathic characteristic which is related to the membrane interaction.[9] The insertion of Protegrin-1 into the lipid layer results in the disordering of lipid packing to the membrane disruption.[13]
Antimicrobial Activity
The protegrins are highly microbicidal against Candida albicans,[14] Escherichia coli,[15]Listeria monocytogenes, Neisseria gonorrhoeae[16] , and the virions of the human immunodeficiency virus in vitro under conditions which mimic the tonicity of the extracellular milieu.[1][5][17] The mechanism of this microbicidal activity is believed to involve membrane disruption, similar to many other antibiotic peptides [5][18]
References
 |
Wikimedia Commons has media related to Protegrins. |
- ↑ 1.0 1.1 1.2 Lua error in package.lua at line 80: module 'strict' not found.
- ↑ Lua error in package.lua at line 80: module 'strict' not found.
- ↑ Lua error in package.lua at line 80: module 'strict' not found.
- ↑ Lua error in package.lua at line 80: module 'strict' not found.
- ↑ 5.0 5.1 5.2 5.3 5.4 Lua error in package.lua at line 80: module 'strict' not found.
- ↑ Lua error in package.lua at line 80: module 'strict' not found.
- ↑ Lua error in package.lua at line 80: module 'strict' not found.
- ↑ Lua error in package.lua at line 80: module 'strict' not found.
- ↑ 9.0 9.1 Lua error in package.lua at line 80: module 'strict' not found.
- ↑ Lua error in package.lua at line 80: module 'strict' not found.
- ↑ Lua error in package.lua at line 80: module 'strict' not found.
- ↑ Lua error in package.lua at line 80: module 'strict' not found.
- ↑ 13.0 13.1 Lua error in package.lua at line 80: module 'strict' not found.
- ↑ Lua error in package.lua at line 80: module 'strict' not found.
- ↑ Lua error in package.lua at line 80: module 'strict' not found.
- ↑ Lua error in package.lua at line 80: module 'strict' not found.
- ↑ Lua error in package.lua at line 80: module 'strict' not found.
- ↑ Lua error in package.lua at line 80: module 'strict' not found.
