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But free-floating heme may also play an important biological role, according to a new study. Authors recently showed that free heme can bind to and inhibit the action of a calcium-dependent potassium channel. Author s team began to investigate the interaction of heme with this channel after an analysis of its amino acid sequence turned up a known heme-binding motif. This motif, which contains two cysteines and a histidine, is located in the portion of the potassium channel that protrudes into the cytoplasm between the domains that are thought to regulate channel opening. Sure enough, Author s team found that heme does bind to this motif. Electron paramagnetic resonance and UV-visible spectra of heme bound to a 23-residue peptide fragment encompassing the motif suggest that the histidine side chain coordinates to the heme's iron center. This mode of heme coordination is similar to that seen in cytochrome proteins. Using electrophysiological techniques to monitor the ability of single channels to transport potassium ions across membranes, Author s team has shown that heme binding inhibits the channel's function by decreasing the frequency of channel openings. In vivo, free heme--high concentrations of which are released after strokes, heart attacks, and other severe injuries--may block this potassium channel, preventing it from carrying out its normal cell-protective duties. Nobody expected that free heme might play such a role. But "now that we have provided the first example of a fast heme-signaling system, other examples are likely to follow," he tells. His team is currently trying to test whether these channels are tagged with heme after cellular injury. these ligands could be used to "dial in" channel specificity to selectively modulate the action of specific channels in vivo. |
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