PROTO_POLPI
ID PROTO_POLPI Reviewed; 12 AA.
AC P0C1R0; P84879;
DT 25-JUL-2006, integrated into UniProtKB/Swiss-Prot.
DT 25-JUL-2006, sequence version 1.
DT 29-SEP-2021, entry version 21.
DE RecName: Full=Polybia-CP {ECO:0000303|PubMed:16129513, ECO:0000303|PubMed:30534613, ECO:0000303|PubMed:32360153};
DE AltName: Full=Pol-CP-NH2 {ECO:0000303|PubMed:30534613, ECO:0000303|PubMed:32360153};
DE AltName: Full=Polybia chemotactic peptide {ECO:0000303|PubMed:16129513};
OS Polybia paulista (Neotropical social wasp) (Swarm-founding polistine wasp).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Hymenoptera; Apocrita; Aculeata; Vespoidea;
OC Vespidae; Polistinae; Epiponini; Polybia.
OX NCBI_TaxID=291283;
RN [1]
RP PROTEIN SEQUENCE, FUNCTION, SUBCELLULAR LOCATION, MASS SPECTROMETRY, AND
RP AMIDATION AT LEU-12.
RC TISSUE=Venom;
RX PubMed=16129513; DOI=10.1016/j.peptides.2005.04.026;
RA Souza B.M., Mendes M.A., Santos L.D., Marques M.R., Cesar L.M.M.,
RA Almeida R.N.A., Pagnocca F.C., Konno K., Palma M.S.;
RT "Structural and functional characterization of two novel peptide toxins
RT isolated from the venom of the social wasp Polybia paulista.";
RL Peptides 26:2157-2164(2005).
RN [2]
RP FUNCTION, SUBCELLULAR LOCATION, AND SYNTHESIS.
RX PubMed=21745529; DOI=10.1016/j.tox.2011.06.014;
RA Wang K., Yan J., Liu X., Zhang J., Chen R., Zhang B., Dang W., Zhang W.,
RA Kai M., Song J., Wang R.;
RT "Novel cytotoxity exhibition mode of polybia-CP, a novel antimicrobial
RT peptide from the venom of the social wasp Polybia paulista.";
RL Toxicology 288:27-33(2011).
RN [3]
RP FUNCTION, SUBCELLULAR LOCATION, SYNTHESIS, AND BIOPHYSICOCHEMICAL
RP PROPERTIES.
RX PubMed=22450985; DOI=10.1128/aac.05995-11;
RA Wang K., Yan J., Chen R., Dang W., Zhang B., Zhang W., Song J., Wang R.;
RT "Membrane-active action mode of polybia-CP, a novel antimicrobial peptide
RT isolated from the venom of Polybia paulista.";
RL Antimicrob. Agents Chemother. 56:3318-3323(2012).
RN [4]
RP FUNCTION, AND SYNTHESIS.
RX PubMed=23836163; DOI=10.1128/aac.02311-12;
RA Wang K., Dang W., Yan J., Chen R., Liu X., Yan W., Zhang B., Xie J.,
RA Zhang J., Wang R.;
RT "Membrane perturbation action mode and structure-activity relationships of
RT Protonectin, a novel antimicrobial peptide from the venom of the
RT neotropical social wasp Agelaia pallipes pallipes.";
RL Antimicrob. Agents Chemother. 57:4632-4639(2013).
RN [5]
RP FUNCTION, MUTAGENESIS OF ILE-1; THR-4; ILE-5; LEU-6; GLY-7; LYS-10 AND
RP SER-11, AND PHARMACEUTICAL.
RX PubMed=30534613; DOI=10.1038/s42003-018-0224-2;
RA Torres M.D.T., Pedron C.N., Higashikuni Y., Kramer R.M., Cardoso M.H.,
RA Oshiro K.G.N., Franco O.L., Silva Junior P.I., Silva F.D.,
RA Oliveira Junior V.X., Lu T.K., de la Fuente-Nunez C.;
RT "Structure-function-guided exploration of the antimicrobial peptide
RT polybia-CP identifies activity determinants and generates synthetic
RT therapeutic candidates.";
RL Commun. Biol. 1:221-221(2018).
RN [6]
RP FUNCTION, SYNTHESIS, AND PHARMACEUTICAL.
RX PubMed=32360153; DOI=10.1016/j.toxicon.2020.04.099;
RA Freire K.A., Torres M.T., Lima D.B., Monteiro M.L.,
RA Bezerra de Menezes R.R.P.P., Martins A.M.C., Oliveira V.X. Jr.;
RT "Wasp venom peptide as a new antichagasic agent.";
RL Toxicon 181:71-78(2020).
CC -!- FUNCTION: Potent antimicrobial peptide that is active against both
CC Gram-positive and Gram-negative bacteria (B.subtilis (MIC=15 ug/ml or
CC 4-16 uM), S.epidermidis (MIC=8-16 uM), S.aureus (MIC=15 ug/ml or 4 uM),
CC E.coli (MIC=8-64 uM) and P.aeruginosa (MIC=64-128 uM))
CC (PubMed:16129513, PubMed:22450985, PubMed:23836163, PubMed:30534613).
CC Also shows cytotoxicity towards HEK293 cells (32 uM) (PubMed:30534613).
CC Adopts an amphipathic alpha helical conformation, that may allow to
CC partition into the target membrane (PubMed:21745529, PubMed:23836163).
CC Acts by disrupting bacterial membrane (PubMed:21745529,
CC PubMed:22450985). Also acts in inflammation since it is chemotactic for
CC polymorphonucleated leukocytes (PMNL) (PubMed:16129513). Shows potent
CC antitumor activity against prostate and bladder cancer cell lines
CC (PubMed:21745529). Causes a reduced hemolysis to mammalian erythrocytes
CC (HC(50)=50 uM) and has no mast cell degranulation activity at
CC physiological concentrations (PubMed:16129513, PubMed:30534613). In
CC addition, when tested in vitro on the parasite Trypanosoma cruzi
CC (responsible of the Chagas disease), is able to reduce the number of
CC the three forms (epimastigote, trypomastigote and amastigote), probably
CC acting through the apoptotic cell death pathway (PubMed:32360153).
CC {ECO:0000269|PubMed:16129513, ECO:0000269|PubMed:21745529,
CC ECO:0000269|PubMed:22450985, ECO:0000269|PubMed:23836163,
CC ECO:0000269|PubMed:30534613, ECO:0000269|PubMed:32360153}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Temperature dependence:
CC Is stable between 20 and 100 degrees Celsius.
CC {ECO:0000269|PubMed:22450985};
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16129513}. Target
CC cell membrane {ECO:0000269|PubMed:21745529,
CC ECO:0000269|PubMed:22450985}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:16129513}.
CC -!- MASS SPECTROMETRY: Mass=1239.73; Method=Electrospray;
CC Evidence={ECO:0000269|PubMed:16129513};
CC -!- PHARMACEUTICAL: Promising drug candidate or lead for the development of
CC new drugs to treat Chagas disease (also called American
CC Trypanosomiasis). {ECO:0000305|PubMed:32360153}.
CC -!- PHARMACEUTICAL: The [Lys]7-Pol-CP-NH2 analog is a promising drug lead
CC for the treatment of drug-resistant infection. It demonstrates anti-
CC infective activity aginst P.aeruginosa, when tested in vivo on a skin
CC infection mice model. {ECO:0000305|PubMed:30534613}.
CC -!- SIMILARITY: Belongs to the MCD family. Protonectin subfamily.
CC {ECO:0000305}.
CC -!- WEB RESOURCE: Name=The antimicrobial peptide database;
CC URL="https://wangapd3.com/database/query_output.php?ID=00542";
CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=A wasp's sting - Issue 229
CC of October 2020;
CC URL="https://web.expasy.org/spotlight/back_issues/229/";
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DR GO; GO:0005576; C:extracellular region; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-KW.
DR GO; GO:0006935; P:chemotaxis; IEA:UniProtKB-KW.
DR GO; GO:0050829; P:defense response to Gram-negative bacterium; IDA:UniProtKB.
DR GO; GO:0050830; P:defense response to Gram-positive bacterium; IDA:UniProtKB.
DR GO; GO:0050921; P:positive regulation of chemotaxis; IDA:UniProtKB.
PE 1: Evidence at protein level;
KW Amidation; Antibiotic; Antimicrobial; Chemotaxis;
KW Direct protein sequencing; Membrane; Pharmaceutical; Secreted;
KW Target cell membrane; Target membrane.
FT PEPTIDE 1..12
FT /note="Polybia-CP"
FT /evidence="ECO:0000269|PubMed:16129513"
FT /id="PRO_0000247269"
FT MOD_RES 12
FT /note="Leucine amide"
FT /evidence="ECO:0000269|PubMed:16129513"
FT MUTAGEN 1
FT /note="I->G: No change in antibacterial activity, complete
FT loss of hemolytic activity, and complete loss in
FT cytotoxicity towards HEK293 cells."
FT /evidence="ECO:0000269|PubMed:30534613"
FT MUTAGEN 4
FT /note="T->A: Increase in antibacterial activity."
FT /evidence="ECO:0000269|PubMed:30534613"
FT MUTAGEN 4
FT /note="T->K: Increase in antibacterial activity, moderate
FT increase in resistance to protease-mediated degradation,
FT complete loss of hemolytic activity, and no change in
FT cytotoxicity towards HEK293 cells."
FT /evidence="ECO:0000269|PubMed:30534613"
FT MUTAGEN 5
FT /note="I->A: Important decrease in antibacterial activity,
FT important decrease in helical content, and complete loss in
FT cytotoxicity towards HEK293 cells."
FT /evidence="ECO:0000269|PubMed:30534613"
FT MUTAGEN 6
FT /note="L->A: Important increase in antibacterial activity
FT and important decrease in helical content."
FT /evidence="ECO:0000269|PubMed:30534613"
FT MUTAGEN 7
FT /note="G->A: Important increase in antibacterial activity,
FT important increase in helical content, and no change in
FT cytotoxicity towards HEK293 cells."
FT /evidence="ECO:0000269|PubMed:30534613"
FT MUTAGEN 7
FT /note="G->K: Important increase in antibacterial activity,
FT increase in helical content, important increase in
FT resistance to protease-mediated degradation, increase in
FT hemolytic activity, and weak increase in cytotoxicity
FT towards HEK293 cells."
FT /evidence="ECO:0000269|PubMed:30534613"
FT MUTAGEN 10
FT /note="K->A: Important decrease in antibacterial activity
FT and important decrease in helical content."
FT /evidence="ECO:0000269|PubMed:30534613"
FT MUTAGEN 11
FT /note="S->A: Important increase in antibacterial activity,
FT important increase in helical content, and decrease in
FT cytotoxicity towards HEK293 cells."
FT /evidence="ECO:0000269|PubMed:30534613"
SQ SEQUENCE 12 AA; 1241 MW; 0A6676110A287720 CRC64;
ILGTILGLLK SL
