MOLECULAR MOTIONS WITHIN THE PORE OF VOLTAGE-DEPENDENT SODIUM-CHANNELS

The pores of ion channel proteins are often modeled as static structur es. In this view, selectivity reflects rigidly constrained backbone or ientations. Such a picture is at variance with the generalization that biological proteins are flexible, capable of major internal motions o n biologically relevant time scales. We tested for motions in the sodi um channel pore by systematically introducing pairs of cysteine residu es throughout the pore-lining segments. Two distinct pairs of residues spontaneously formed disulfide bonds bridging domains I and II. Nine other permutations, involving all four domains, were capable of disulf ide bonding in the presence of a redox catalyst, The results are incon sistent with a single fixed backbone structure for the pore; instead, the segments that line the permeation pathway appear capable of sizabl e motions.