The alpha-helix and the organization and gating of channels.
The structures of an increasing number of channels and other alpha-helical membrane proteins have been determined recently, including the KcsA potassium channel, the MscL mechanosensitive channel, and the AQP1 and GlpF members of the aquaporin family. In this chapter, the orientation and packing characteristics of bilayer-spanning helices are surveyed in integral membrane proteins. In the case of channels, alpha-helices create the sealed barrier that separates the hydrocarbon region of the bilayer from the permeation pathway for solutes. The helices surrounding the permeation pathway tend to be rather steeply tilted relative to the membrane normal and are consistently arranged in a right-handed bundle. The helical framework further provides a supporting scaffold for nonmembrane-spanning structures associated with channel selectivity. Although structural details remain scarce, the conformational changes associated with gating transitions between closed and open states of channels are reviewed, emphasizing the potential roles of helix-helix interactions in this process.
Spencer
Robert H
RH
Department of Pharmacology, Merck Research Laboratories, West Point, PA 19486. rob_spencer@merck.com
Rees
Douglas C
DC
D000818:Animals; D020346:Aquaporins / Q000737:chemistry; D002462:Cell Membrane / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000737:chemistry; D007473:Ion Channels / Q000737:chemistry*; D007477:Ions; D008958:Models, Molecular; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary
D020346:Aquaporins; D029968:Escherichia coli Proteins; D007473:Ion Channels; D007477:Ions; C086596:MscL protein, E coli; C078043:GlpF protein, E coli