| 1. |
- Basmarke-Wehelie, Rahma, et al.
(författare)
-
The complement regulator CD46 is bactericidal to Helicobacter pylori and blocks urease activity
- 2011
-
Ingår i: Gastroenterology. - Baltimore : Elsevier BV. - 0016-5085 .- 1528-0012. ; 141:3, s. 918-928
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND & AIMS: CD46 is a C3b/C4b binding complement regulator and a receptor for several human pathogens. We examined the interaction between CD46 and Helicobacter pylori (a bacterium that colonizes the human gastric mucosa and causes gastritis), peptic ulcers, and cancer.METHODS: Using gastric epithelial cells, we analyzed a set of H pylori strains and mutants for their ability to interact with CD46 and/or influence CD46 expression. Bacterial interaction with full-length CD46 and small CD46 peptides was evaluated by flow cytometry, fluorescence microscopy, enzyme-linked immunosorbent assay, and bacterial survival analyses.RESULTS: H pylori infection caused shedding of CD46 into the extracellular environment. A soluble form of CD46 bound to H pylori and inhibited growth, in a dose- and time-dependent manner, by interacting with urease and alkyl hydroperoxide reductase, which are essential bacterial pathogenicity-associated factors. Binding of CD46 or CD46-derived synthetic peptides blocked the urease activity and ability of bacteria to survive in acidic environments. Oral administration of one CD46 peptide eradicated H pylori from infected mice.CONCLUSIONS: CD46 is an antimicrobial agent that can eradicate H pylori. CD46 peptides might be developed to treat H pylori infection.
|
|
| 2. |
- Jurkowski, Wiktor, et al.
(författare)
-
Ligand binding properties of human galanin receptors
- 2013
-
Ingår i: Molecular membrane biology. - : Informa UK Limited. - 0968-7688 .- 1464-5203. ; 30:2, s. 206-216
-
Tidskriftsartikel (refereegranskat)abstract
- The galanin receptor family comprises of three members, GalR1, GalR2 and GalR3, all belonging to the G-protein-couple receptor superfamily. All three receptors bind the peptide hormone galanin, but show distinctly different binding properties to other molecules and effects on intracellular signaling. To gain insight on the molecular basis of receptor subtype specificity, we have generated a three-dimensional model for each of the galanin receptors based on its homologs in the same family. We found significant differences in the organization of the binding pockets among the three types of receptors, which might be the key for specific molecular recognition of ligands. Through docking of fragments of the galanin peptide and a number of ligands, we investigated the involvement of transmembrane and loop residues in ligand interaction.
|
|
| 3. |
- Runesson, Johan, 1980-, et al.
(författare)
-
Determining receptor–ligand interaction of human galanin receptor type 3
- 2010
-
Ingår i: Neurochemistry International. - : Elsevier BV. - 0197-0186 .- 1872-9754. ; 57:7, s. 804-811
-
Tidskriftsartikel (refereegranskat)abstract
- Galanin is a neuropeptide found throughout the central and peripheral nervous systems of a wide range of species, ranging from human and mouse to frog and tuna. Galanin mediates its physiological roles through three receptors (GalR1–3), all members of the G-protein coupled receptor family. In mapping these roles, receptor subtype selective ligands are crucial tools. To facilitate the ligand design, data on receptor structure and interaction points are of great importance. The current study investigates the mechanism by which galanin interacts with GalR3. Mutated receptors were tested with competitive binding analysis in vitro. Our studies identify six mutagenic constructs that lost receptor affinity completely, despite being expressed at the cell surface. Mutations of the Tyr1033.33 in transmembrane helix (TM) III, His2516.51 in TM VI, Arg2737.35 or His2777.39 in TM VII, Phe2636.63 or Tyr2707.32 in the extracellular loop III all result in complete reduction of ligand binding. In addition, docking studies of an in silico model of GalR3 propose that four of the identified residues interact with pharmacophores situated within the galanin(2–6) sequence. This study provides novel insights into the interaction between ligands and GalR3 and highlights the requirement for correct design of targeting ligands.
|
|
