Lipids tell channel to open wide
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《细胞学杂志》
Martinac/Macmillan
Structural studies of a bacterial ion channel in a new article by Eduardo Perozo (University of Virginia, Charlottesville, VA), Boris Martinac (University of Western Australia, Crawley, Australia), and colleagues reveal how the channel senses when to open through interactions with membrane lipids.
Mechanosensitive channels, such as bacterial MscL studied by Perozo, open when the pressure inside a cell increases, thus allowing the passage of ions and other solutes. MscL needs only a lipid environment to respond to pressure, indicating that interactions between lipids and channel proteins are sufficient to regulate channel structure. The new study reveals that a change in intramembrane pressure rather than membrane thinning is the key determinant for channel opening.
As tension grows in the cell, the bilayer thins, possibly exposing hydrophobic amino acids of the channel to the aqueous environment. Perozo et al. mimicked this effect using lipids of various acyl chain lengths. Shorter chains (i.e., thinner membranes) primed the channel for opening by smaller pressures, but did not open the channel.
Increasing pressure within the cell may also place more pressure on the outer head-groups of membrane lipids and less pressure in the acyl chain regions. Sure enough, the channel did open upon mixing cone-shaped lipids into the bilayer, which should mimic the effect of pressurized cytosol on lipid heads.
Another paper, by Monica Betanzos, Shergei Sukharev (University of Maryland, College Park, MD), and colleagues, examined how the proteins of the channel rearrange upon opening. Each of the four subunits of one MscL channel contains two transmembrane (TM) domains, TM1 lining the pore and TM2 on the periphery. Sukharev's group found that the TM domains together tilt outward in response to osmotic shock, widening the pore like the opening of an iris. This model is consistent with that recently demonstrated in a second paper by Perozo and colleagues.
References:
Perozo, E., et al. 2002. Nat. Struct. Biol. 10.1038/nsb827.
Betanzos, M., et al. 2002. Nat. Struct. Biol. 10.1038/nsb828.
Perozo, E., et al. 2002 Nature. 10.1038/nature00992.(Lipid addition (arrow) opens MscL withou)
Structural studies of a bacterial ion channel in a new article by Eduardo Perozo (University of Virginia, Charlottesville, VA), Boris Martinac (University of Western Australia, Crawley, Australia), and colleagues reveal how the channel senses when to open through interactions with membrane lipids.
Mechanosensitive channels, such as bacterial MscL studied by Perozo, open when the pressure inside a cell increases, thus allowing the passage of ions and other solutes. MscL needs only a lipid environment to respond to pressure, indicating that interactions between lipids and channel proteins are sufficient to regulate channel structure. The new study reveals that a change in intramembrane pressure rather than membrane thinning is the key determinant for channel opening.
As tension grows in the cell, the bilayer thins, possibly exposing hydrophobic amino acids of the channel to the aqueous environment. Perozo et al. mimicked this effect using lipids of various acyl chain lengths. Shorter chains (i.e., thinner membranes) primed the channel for opening by smaller pressures, but did not open the channel.
Increasing pressure within the cell may also place more pressure on the outer head-groups of membrane lipids and less pressure in the acyl chain regions. Sure enough, the channel did open upon mixing cone-shaped lipids into the bilayer, which should mimic the effect of pressurized cytosol on lipid heads.
Another paper, by Monica Betanzos, Shergei Sukharev (University of Maryland, College Park, MD), and colleagues, examined how the proteins of the channel rearrange upon opening. Each of the four subunits of one MscL channel contains two transmembrane (TM) domains, TM1 lining the pore and TM2 on the periphery. Sukharev's group found that the TM domains together tilt outward in response to osmotic shock, widening the pore like the opening of an iris. This model is consistent with that recently demonstrated in a second paper by Perozo and colleagues.
References:
Perozo, E., et al. 2002. Nat. Struct. Biol. 10.1038/nsb827.
Betanzos, M., et al. 2002. Nat. Struct. Biol. 10.1038/nsb828.
Perozo, E., et al. 2002 Nature. 10.1038/nature00992.(Lipid addition (arrow) opens MscL withou)