Browse
Submit Data
Databases
API
Help

Dataset Information

14 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Human salivary MUC7 mucin peptides: effect of size, charge and cysteine residues on antifungal activity.

ABSTRACT: We have previously shown that MUC7 (human salivary low-molecular-mass mucin) 20-mer: LAHQKPFIRKSYKCLHKRCR (residues 32-51 of the parent MUC7, with a net positive charge of 7) possesses a broad-spectrum antimicrobial activity [Bobek and Situ (2003) Antimicrob. Agents Chemother. 47, 645-652]. The aims of the present study were to determine the minimum peptide chain length and its location within the 20-mer region that retains potent antifungal activity against Candida albicans and Cryptococcus neoformans and to examine the effect of net charge of the peptide as well as the role of cysteine residues on the fungicidal activity. First, several C-terminal truncated MUC7 20-mer fragments (16-mer, 12-mer, 11-mer, 10-mer and 8-mer) and one N-terminal fragment (8-mer-N) were synthesized and tested. The results showed that MUC7 12-mer, located at the C-terminal region of MUC7 20-mer, having a net charge of +6 and exhibiting an amphipathic helical conformation, not only retained but exceeded the antifungal activity of that of 20-mer. Secondly, several variants of the 12-mer peptide containing a lower or no net positive charge, or no cysteine residues were synthesized and tested. A clear correlation between the net positive charge of the 12-mer, its potency and initial interaction of peptide with fungal cells was found by killing assays, fluorescence microscopy and fungal cell-membrane potential measurements. Furthermore, cysteine residues, which play a critical role in bacterial binding, were found to be not important for the fungicidal activity of these peptides. These results identified MUC7 12-mer as a potential candidate for development into a novel antifungal therapeutic agent.

SUBMITTER: Situ H

PROVIDER: S-EPMC1223654 | biostudies-other | 2003 Oct

REPOSITORIES: biostudies-other

ACCESS DATA

Json Xml

Similar Datasets

Metal Binding Ability of Small Peptides Containing Cysteine Residues.

Project description:The Cd(II)-, Pb(II)-, Ni(II)- and Zn(II)-complexes of small terminally protected peptides containing CXXX, XXXC, XCCX, CXn C (n=1-3) sequences have been studied with potentiometric, UV/Vis and CD spectroscopic techniques. The cysteine thiolate group is the primary binding site for all studied metal ions, but the presence of a histidyl or aspartyl side chain in the molecule contributes to the stability of the complexes. For two-cysteine containing peptides the (S- ,S- ) coordinated species are formed in the physiological pH range and the stability increases in the Ni(II)<Zn(II)<Pb(II)<Cd(II) order. As a conclusion, the inserting of -CXXC- sequence into the peptide makes the synthesis of peptides with high selectivity to toxic Cd(II) or Pb(II) ion possible. In addition, the spectroscopic characterization of these complexes can contribute to the discovery of the exact binding site and binding mode of longer peptides mimicking the biologically important proteins.

| S-EPMC8028610 | biostudies-literature

Cysteine mutagenesis reveals transmembrane residues associated with charge translocation in prestin.

Project description:The solute carrier transmembrane protein prestin (SLC26A5) drives an active electromechanical transduction process in cochlear outer hair cells that increases hearing sensitivity and frequency discrimination in mammals. A large intramembraneous charge movement, the nonlinear capacitance (NLC), is the electrical signature of prestin function. The transmembrane domain (TMD) helices and residues involved in the intramembrane charge displacement remain unknown. We have performed cysteine-scanning mutagenesis with serine or valine replacement to investigate the importance of cysteine residues to prestin structure and function. The distribution of oligomeric states and membrane abundance of prestin was also probed to investigate whether cysteine residues participate in prestin oligomerization and/or NLC. Our results reveal that 1) Cys-196 (TMD 4) and Cys-415 (TMD 10) do not tolerate serine replacement, and thus maintaining hydrophobicity at these locations is important for the mechanism of charge movement; 2) Cys-260 (TMD 6) and Cys-381 (TMD 9) tolerate serine replacement and are probably water-exposed; and 3) if disulfide bonds are present, they do not serve a functional role as measured via NLC. These novel findings are consistent with a recent structural model, which proposes that prestin contains an occluded aqueous pore, and we posit that the orientations of transmembrane domain helices 4 and 10 are essential for proper prestin function.

| S-EPMC2823402 | biostudies-literature

Delivery of a mucin domain enriched in cysteine residues strengthens the intestinal mucous barrier.

Project description:A weakening of the gut mucous barrier permits an increase in the access of intestinal luminal contents to the epithelial cells, which will trigger the inflammatory response. In inflammatory bowel diseases, there is an inappropriate and ongoing activation of the immune system, possibly because the intestinal mucus is less protective against the endogenous microflora. General strategies aimed at improving the protection of the intestinal epithelium are still missing. We generated a transgenic mouse that secreted a molecule consisting of 12 consecutive copies of a mucin domain into its intestinal mucus, which is believed to modify the mucus layer by establishing reversible interactions. We showed that the mucus gel was more robust and that mucin O-glycosylation was altered. Notably, the gut epithelium of transgenic mice housed a greater abundance of beneficial Lactobacillus spp. These modifications were associated with a reduced susceptibility of transgenic mice to chemically induced colitis. Furthermore, transgenic mice cleared faster Citrobacter rodentium bacteria which were orally given and mice were more protected against bacterial translocation induced by gavage with adherent-invasive Escherichia coli. Our data show that delivering the mucin CYS domain into the gut lumen strengthens the intestinal mucus blanket which is impaired in inflammatory bowel diseases.

| S-EPMC4431476 | biostudies-literature

Selective and Reversible Photochemical Derivatization of Cysteine Residues in Peptides and Proteins.

Project description:Selective derivatization of solvent-exposed cysteine residues in peptides and proteins is achieved by brief irradiation of an aqueous solution containing 3-(hydroxymethyl)-2-naphthol derivatives (NQMPs) with 350 nm fluorescent lamp. NQMP can be conjugated with various moieties, such as PEG, dyes, carbohydrates, or possess a fragment for further selective derivatization, e.g., biotin, azide, alkyne, etc. Attractive features of this labeling approach include an exceptionally fast rate of the reaction and a requirement for low equivalence of the reagent. The NQMP-thioether linkage is stable under ambient conditions, survives protein digestion and MS analysis. Irradiation of NQMP-labeled protein in a dilute solution (<40 ?M) or in the presence of a vinyl ether results in a traceless release of the substrate. The reversible biotinylation of bovine serum albumin, as well as capture and release of this protein using NeutrAvidin Agarose resin beads has been demonstrated.

| S-EPMC3994131 | biostudies-literature

Design, Synthesis and Antifungal Activity of Stapled Aurein1.2 Peptides.

Project description:Aurein1.2 is a 13-residue antimicrobial peptide secreted by the Australian tree frog Litoria aurea. In order to improve its stabilities, the helical contents and corresponding biological activities of Aurein1.2 (a series of stapled analogues) were synthesized, and their potential antifungal activities were evaluated. Not surprisingly, the stapled Aurein1.2 peptides showed higher proteolytic stability and helicity than the linear counterpart. The minimum inhibitory concentration (MIC) of ten stapled peptides against six strains of common pathogenic fungi was determined by the microscale broth dilution method recommended by CLSI. Of them, Sau-1, Sau-2, Sau-5, and Sau-9 exhibited better inhibitory effects on the fungi than the linear peptide. These stapled Aurein1.2 peptides may serve as the leading compounds for further optimization and antifungal therapy.

| S-EPMC8389037 | biostudies-literature

The properties conferred upon triple-helical collagen-mimetic peptides by the presence of cysteine residues.

Project description:Recently, the ability of polymeric collagen-like peptides to regulate cell behavior has generated great interest. A triple-helical peptide known as collagen-related peptide (CRP) contains the sequence (Gly-Pro-Hyp)(10). With Gly-Pro-Cys triplets appended to both of its termini, designated CRP(cys), chemical cross-linking using heterobifunctional reagents generates CRP(cys)-XL, a potent, widely used, polymeric agonist for platelet Glycoprotein VI, whereas non-cross-linked, monomeric CRP(cys) antagonizes Glycoprotein VI. Here, we describe how cysteine in these triplets may also undergo random air-induced oxidation, especially upon prolonged storage or repeated freeze-thawing, to form disulphide bonds, resulting in a lesser degree of polymerization than with chemical cross-linking. We investigated the monomeric and polymeric states of these and other cysteine-containing collagen-derived peptides, using gel filtration and dynamic light scattering, allowing the size of a CRP-XL aggregate to be estimated. The effect of cysteine thiols upon peptide adsorption to surfaces and subsequent platelet responses was investigated. This demonstrated that cysteine is required for strong binding to glass coverslips and to plastic plates used in ELISA assays.

| S-EPMC3491313 | biostudies-literature

Two immunoregulatory peptides with antioxidant activity from tick salivary glands.

Project description:Ticks are blood-feeding arthropods that may secrete immunosuppressant molecules, which inhibit host inflammatory and immune responses and provide survival advantages to pathogens at tick bleeding sites in hosts. In the current work, two families of immunoregulatory peptides, hyalomin-A and -B, were first identified from salivary glands of hard tick Hyalomma asiaticum asiaticum. Three copies of hyalomin-A are encoded by an identical gene and released from the same protein precursor. Both hyalomin-A and -B can exert significant anti-inflammatory functions, either by directly inhibiting host secretion of inflammatory factors such as tumor necrosis factor-alpha, monocyte chemotectic protein-1, and interferon-gamma or by indirectly increasing the secretion of immunosuppressant cytokine of interleukin-10. Hyalomin-A and -B were both found to potently scavenge free radical in vitro in a rapid manner and inhibited adjuvant-induced inflammation in mouse models in vivo. The JNK/SAPK subgroup of the MAPK signaling pathway was involved in such immunoregulatory functions of hyalomin-A and -B. These results showed that immunoregulatory peptides of tick salivary glands suppress host inflammatory response by modulating cytokine secretion and detoxifying reactive oxygen species.

| S-EPMC2878058 | biostudies-literature

Recent evolution of the salivary mucin MUC7.

Project description:Genomic structural variants constitute the majority of variable base pairs in primate genomes and affect gene function in multiple ways. While whole gene duplications and deletions are relatively well-studied, the biology of subexonic (i.e., within coding exon sequences), copy number variation remains elusive. The salivary MUC7 gene provides an opportunity for studying such variation, as it harbors copy number variable subexonic repeat sequences that encode for densely O-glycosylated domains (PTS-repeats) with microbe-binding properties. To understand the evolution of this gene, we analyzed mammalian and primate genomes within a comparative framework. Our analyses revealed that (i) MUC7 has emerged in the placental mammal ancestor and rapidly gained multiple sites for O-glycosylation; (ii) MUC7 has retained its extracellular activity in saliva in placental mammals; (iii) the anti-fungal domain of the protein was remodified under positive selection in the primate lineage; and (iv) MUC7 PTS-repeats have evolved recurrently and under adaptive constraints. Our results establish MUC7 as a major player in salivary adaptation, likely as a response to diverse pathogenic exposure in primates. On a broader scale, our study highlights variable subexonic repeats as a primary source for modular evolutionary innovation that lead to rapid functional adaptation.

| S-EPMC4997351 | biostudies-literature

Effect of ring size on conformation and biological activity of cyclic cationic antimicrobial peptides.

Project description:In a series of cyclic peptides based on GS10, an analogue of gramicidin S (GS), the ring size was varied from 10 to 16 amino acids. Alternative addition of basic and hydrophobic amino acids to the original GS10 construct generated a variety of even-numbered rings, i.e., GS10 [cyclo-(VKLdYPVKLdYP)], GS12 [cyclo-(VKLKdYPKVKLdYP)], GS14 [cyclo-(VKLKVdYPLKVKLdYP), and GS16 [cyclo-(VKLKVKdYPKLKVKLdYP)] (d stands for d-enantiomers). The odd-numbered analogues (11-, 13-, and 15-mers) were derived from these four peptides by either addition or deletion of single basic (Lys) or hydrophobic (Leu or Val) amino acids. The resulting peptides, divided into three groups on the basis of peptide ring size (10- to 12-meric, 13- and 14-meric, and 15- and 16-meric), illustrated a diverse spectrum of biological activity correlated to their ring size, degree of beta-structure disruption, charge, hydrophobicity, amphipathicity, and affinity for lipid membranes. Two of these peptides with potent antimicrobial activities and high therapeutic indexes (4.5- to 10-fold compared with GS) are promising candidates for development of broad-spectrum antibiotics.

| S-EPMC2759687 | biostudies-other

Streptococcus gordonii transcriptional response to salivary mucin

Project description:All organisms throughout the tree of life sense and respond to their surface environments. To discriminate from among mucosal surface environmental cues, we grew Streptococcus gordonii biofilms over night at 37C on surfaces coated with the salivary mucin MUC5B, or a low density protein fraction derived from human saliva.

2022-05-05 | GSE202049 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data