UPE35_UPEMJ
ID UPE35_UPEMJ Reviewed; 17 AA.
AC P82042;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 30-MAY-2000, sequence version 1.
DT 25-MAY-2022, entry version 47.
DE RecName: Full=Uperin-3.5 {ECO:0000303|Ref.1};
OS Uperoleia mjobergii (Mjoberg's toadlet) (Pseudophryne mjobergii).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Anura; Neobatrachia; Myobatrachoidea; Myobatrachidae;
OC Myobatrachinae; Uperoleia.
OX NCBI_TaxID=104954;
RN [1]
RP PROTEIN SEQUENCE, FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY,
RP AMIDATION AT VAL-17, AND MASS SPECTROMETRY.
RC TISSUE=Skin secretion;
RA Bradford A.M., Bowie J.H., Tyler M.J., Wallace J.C.;
RT "New antibiotic uperin peptides from the dorsal glands of the australian
RT toadlet Uperoleia mjobergii.";
RL Aust. J. Chem. 49:1325-1331(1996).
RN [2]
RP SYNTHESIS, AND SUBUNIT.
RX PubMed=26676975; DOI=10.1002/cbic.201500518;
RA Calabrese A.N., Liu Y., Wang T., Musgrave I.F., Pukala T.L., Tabor R.F.,
RA Martin L.L., Carver J.A., Bowie J.H.;
RT "The Amyloid Fibril-Forming Properties of the Amphibian Antimicrobial
RT Peptide Uperin 3.5.";
RL ChemBioChem 17:239-246(2016).
RN [3]
RP FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, AND MUTAGENESIS OF GLY-1; ASP-4
RP AND ARG-7.
RX DOI=10.1002/pep2.24052;
RA Martin L.L., Kubeil C., Piantavigna S., Tikkoo T., Gray N.P., John T.,
RA Calabrese A.N., Lui Y., Hong Y., Hossain M.A., Patil N.A., Abel B.,
RA Hoffmann R., Bowie J.H., Carver J.A.;
RT "Amyloid aggregation and membrane activity of the antimicrobial peptide
RT uperin 3.5.";
RL Pept. Sci. 110:1-9(2018).
RN [4]
RP SYNTHESIS, SUBUNIT, AND MUTAGENESIS OF GLY-1; ASP-4 AND ARG-7.
RX PubMed=31385514; DOI=10.1021/acs.biochem.9b00536;
RA John T., Dealey T.J.A., Gray N.P., Patil N.A., Hossain M.A., Abel B.,
RA Carver J.A., Hong Y., Martin L.L.;
RT "The Kinetics of Amyloid Fibrillar Aggregation of Uperin 3.5 Is Directed by
RT the Peptide's Secondary Structure.";
RL Biochemistry 58:3656-3668(2019).
RN [5] {ECO:0007744|PDB:6GS3}
RP X-RAY CRYSTALLOGRAPHY (1.45 ANGSTROMS), SYNTHESIS, FUNCTION,
RP BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, AND SUBCELLULAR LOCATION.
RX PubMed=33431675; DOI=10.1073/pnas.2014442118;
RA Salinas N., Tayeb-Fligelman E., Sammito M.D., Bloch D., Jelinek R., Noy D.,
RA Uson I., Landau M.;
RT "The amphibian antimicrobial peptide uperin 3.5 is a cross-alpha/cross-beta
RT chameleon functional amyloid.";
RL Proc. Natl. Acad. Sci. U.S.A. 118:0-0(2021).
CC -!- FUNCTION: Shows antibacterial activity against B.cereus, L.lactis,
CC L.innocua, M.luteus, S.aureus, P.multoci, S.hominis, S.epidermidis and
CC S.uberis (Ref.1, PubMed:33431675). Strong activity against M.luteus
CC (MIC=2 uM) compared to S.hominis, S.epidermidis and S.aureus
CC (PubMed:33431675). Acts by inducing permeabilization of bacterial
CC membranes (PubMed:33431675). Forms amyloid fibrils which, in the
CC presence of bacteria, aggregate on the bacterial membrane leading to
CC severe membrane damage and cell death (Ref.3, PubMed:33431675).
CC {ECO:0000269|PubMed:33431675, ECO:0000269|Ref.1, ECO:0000269|Ref.3}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Temperature dependence:
CC Thermostable (PubMed:33431675). Retains antibacterial activity
CC against M.luteus after heat treatment at 60 degrees Celsius for 10
CC minutes (PubMed:33431675). {ECO:0000269|PubMed:33431675};
CC -!- SUBUNIT: Monomer and homodimer (PubMed:26676975, PubMed:33431675).
CC Assembles into amyloid fibrils (PubMed:26676975, Ref.3,
CC PubMed:31385514, PubMed:33431675). Under lipid-free conditions, mostly
CC forms fibrils with a cross-beta architecture, consisting of stacks of
CC monomeric amphipathic beta-helices arranged in an antiparallel manner
CC (PubMed:26676975, PubMed:31385514, PubMed:33431675). In the presence of
CC bacteria or membrane lipids, fibrils switch to a cross-alpha
CC conformation which may correlate with its antibacterial activity
CC (PubMed:26676975, Ref.3, PubMed:31385514, PubMed:33431675).
CC {ECO:0000269|PubMed:26676975, ECO:0000269|PubMed:31385514,
CC ECO:0000269|PubMed:33431675, ECO:0000269|Ref.3}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|Ref.1}. Target cell
CC membrane {ECO:0000269|PubMed:33431675, ECO:0000269|Ref.3}.
CC Note=Secreted monomers and fibrils appear to be able to interact with
CC target cell membranes. {ECO:0000269|PubMed:33431675,
CC ECO:0000269|Ref.3}.
CC -!- TISSUE SPECIFICITY: Expressed by the skin dorsal glands.
CC {ECO:0000269|Ref.1}.
CC -!- MASS SPECTROMETRY: Mass=1779; Method=FAB; Evidence={ECO:0000269|Ref.1};
CC -!- MISCELLANEOUS: The amyloid fibrils are cytotoxic to PC12 neuronal
CC cells, whereas the native peptide displays relatively weak cytotoxic
CC activity (PubMed:26676975). Interacts with mammal mimetic membranes
CC (DMPC:chol) leading to transmembrane pores (Ref.3).
CC {ECO:0000269|PubMed:26676975, ECO:0000269|Ref.3}.
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DR PDB; 6GS3; X-ray; 1.45 A; A/B=1-17.
DR PDBsum; 6GS3; -.
DR AlphaFoldDB; P82042; -.
DR SMR; P82042; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-KW.
DR GO; GO:0044218; C:other organism cell membrane; IDA:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0051715; P:cytolysis in another organism; IDA:UniProtKB.
DR GO; GO:0050830; P:defense response to Gram-positive bacterium; IDA:UniProtKB.
DR GO; GO:0051673; P:membrane disruption in another organism; IDA:UniProtKB.
DR InterPro; IPR012527; Antimicrobial_8.
DR Pfam; PF08103; Antimicrobial_8; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Amidation; Amphibian defense peptide; Antibiotic;
KW Antimicrobial; Direct protein sequencing; Membrane; Secreted;
KW Target cell membrane; Target membrane.
FT PEPTIDE 1..17
FT /note="Uperin-3.5"
FT /id="PRO_0000043858"
FT SITE 7
FT /note="Involved in inter-helical interactions along the
FT fibril"
FT /evidence="ECO:0000269|PubMed:33431675"
FT MOD_RES 17
FT /note="Valine amide"
FT /evidence="ECO:0000269|Ref.1"
FT MUTAGEN 1
FT /note="G->L: Loss of amyloid fibril formation but no effect
FT on membrane disruption activity against bacterial mimetic
FT membranes (DMPC:DMPG). Displays a significant increase in
FT amyloid fibril formation; when associated with A-7."
FT /evidence="ECO:0000269|PubMed:31385514, ECO:0000269|Ref.3"
FT MUTAGEN 4
FT /note="D->A: Decreased amyloid fibril formation."
FT /evidence="ECO:0000269|PubMed:31385514"
FT MUTAGEN 7
FT /note="R->A: Loss of membrane disruption activity against
FT bacterial mimetic membranes (DMPC:DMPG) and strong increase
FT in amyloid fibril formation. Displays a significant
FT increase in amyloid fibril formation; when associated with
FT L-1."
FT /evidence="ECO:0000269|PubMed:31385514, ECO:0000269|Ref.3"
FT MUTAGEN 7
FT /note="R->K: No effect on membrane disruption activity
FT against bacterial mimetic membranes (DMPC:DMPG) or amyloid
FT fibril formation."
FT /evidence="ECO:0000269|Ref.3"
FT HELIX 2..13
FT /evidence="ECO:0007829|PDB:6GS3"
SQ SEQUENCE 17 AA; 1781 MW; 6F61E483436AD67B CRC64;
GVGDLIRKAV SVIKNIV
