Molecular struture of ion channels_1

Figure 12 each subunit of the kcsa k channel is

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Unformatted text preview: lies that nature had settled upon a very special solution to achieve, rapid, selective K+ conduction across cell membranes." 12 An important feature of charged ions in solution, which has not been mentioned previously, is that water molecules surround each ion. We refer to such ions as being hydrated. The main idea of the selective filter is that it strips the water molecules from the hydrated K+ ion and conducts dehydrated K+ through the filter. The dehydration is a critical step and why it is relevant for the operation of the selectivity filter will be explained below. The structure of the selectivity filter is complex, but the general idea is that its molecular structure has the shape of an oxygenlined tunnel with four K+ binding sites (Fig. 13A and B2). The oxygen linings at the binding sites are formed by negatively charged carbonyl groups at four sites, sites 14, of the filter (a carbonyl group in organic compounds is a carbon atom doubly bonded to an oxygen atom). At each site, negative carbonyl groups protrude into the tunnel, one carbonyl from each of the four subunits (Fig. 13B4). The arrangement is such that a dehydrated K+ fits precisely into a site, embraced by the negativity at each site. Thus, each site in the tunnel interior mimics the embrace of the water molecules that surround the ion in solution. Importantly, a hydrated K+ or a hydrated Na+ ion does not fit into the sites because they are too big. The precise match in the size of the dehydrated K+ ion and the size of the binding sites is the key factor that imparts selectivity to the filter. Figure 13. Detailed view of KcsA K+ channel features. A: Two subunits show major portions of channel including the outer and inner helices, the central cavity the pore helix (red) and the selectivity filter. The inner helix lines the interior of the central cavity and forms part of the activation gate. The selectivity filter is formed by a sequence of amino acids that link the lower portion of the pore helix with the upper portion of the inner helix. The four small black lines protruding into the selectivity filter are binding sites for dehydrated K+ ions and are composed of the signature sequence of amino acids that characterize the pores of all K+ channels. B1: Inverted teepee arrangement of helices in selectivity filter. The selectivity filter is shown from a side view. Two subunits of the channel are shown in side view. Four K+ ions (green balls) are in the selectivity filter and a single K+ ion is in the central cavity. B2: Expanded side view of selectivity filter 13 with four K+ ions (green balls) located at each of the four K+ binding sites. B3: Top view looking into the filter. A K+ ion is in one binding site and is stabilized by the four subunits. B4: cartoon drawing of a hydrated K+ ion as it would occur in solution. The water is stripped as the ion enters the selectivity filter and is stabilized in one binding site by four negatively charged carbonyl groups, one from each subunit. The negatively charged oxygens in each of the carbonyl groups in the filter replicate exactly the negatively charged oxygen groups to which the K+ ion is bound in solution. In its basic form, the channel has three important parts, as illustrated in Fig. 13A. The first is the gate, located on the intracellular part of the channel. The second is a relatively wide central cavity located just above the gate. The third is the selectivity filter, located above the central cavity. The end of the selectivity filter faces the extracellular fluids. The selectivity filter can exist in one of two configurations. In the open configuration the filter conducts ions while in the closed configuration it is "pinched" so that it does not conduct ions (Fig. 14). Whether the filter is in the open or closed configurations is determined by whether the gate is open or closed, for reasons explained below. Lets follow the exact sequence of events to see how the selectivity filter works by first considering the conditions that occur when the gate in closed and then when it is open. Events when the gate is close...
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This note was uploaded on 09/17/2009 for the course BIO 365R taught by Professor Draper during the Spring '08 term at University of Texas at Austin.

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