In this study we attempted to characterize amino acids properties and their possible interactions with the metal ions. In the first part of this study we described the structure of amino acids, its biochemical properties and its role in organism. In the next and the most important part we summarized accessible information about the metals and heavy metals which can form a bond with amino acids. Especially the heavy metals could have really important role in the process of metabolisms of amino acids, but this role is still unknown.
The P2X7 receptor (P2X7R) is a member of the ATP-gated ion channel family that exhibits distinct electrophysiological and pharmacological properties. This includes low sensitivity to ATP, lack of desensitization, a sustained current growth during prolonged receptor stimulation accompanied with development of permeability to large organic cations, and the coupling of receptor activation to cell blebbing and death. The uniquely long C-terminus of P2X7R accounts for many of these receptor-specific functions. The aim of this study was to understand the role of conserved ectodomain cysteine residues in P2X7R function. Single- and double-point threonine mutants of C119-C168, C129-C152, C135-C162, C216-C226, and C260-C269 cysteine pairs were expressed in HEK293 cells and studied using whole-cell current recording. All mutants other than C119T-P2X7R responded to initial and subsequent application of 300-μM BzATP and ATP with small amplitude monophasic currents or were practically nonfunctional. The mutagenesis-induced loss of function was due to decreased cell-surface receptor expression, as revealed by assessing levels of biotinylated mutants. Coexpression of all double mutants with the wild-type receptor had a transient or, in the case of C119T/C168T double mutant, sustained inhibitory effect on receptor trafficking. The C119T-P2X7R mutant was expressed on the plasma membrane and was fully functional with a slight decrease in the sensitivity for BzATP, indicating that interaction of liberated Cys168 with another residue rescues the trafficking of receptor. Thus, in contrast to other P2XRs, all disulfide bonds of P2X7R are individually essential for the proper receptor trafficking.
- MeSH
- cystein biosyntéza genetika fyziologie MeSH
- HEK293 buňky MeSH
- konzervovaná sekvence * MeSH
- krysa rodu rattus MeSH
- lidé MeSH
- mutace fyziologie MeSH
- purinergní receptory P2X7 genetika metabolismus MeSH
- transport proteinů fyziologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Intramural MeSH
- MeSH
- cystein fyziologie MeSH
- Saccharomyces cerevisiae fyziologie MeSH
- Publikační typ
- srovnávací studie MeSH
