Pore loop

Inward Rectifier K Channels. Figure 4 Kir channel subunits consist of two transmembrane domains (M1, M2), separated by a pore loop (P-loop) that contains the signature K+-selectivity sequence (-GYG-), as well as extended cytoplasmic N - and C-termini. Several residues (indicated) have been implicated in causing rectification (see text). 

D, shown in bold in Fig. 1 bottom) in the pore loop of TRPV5, which is conserved in TRPV6, but not in the other members of the TRPV subfamily, has been shown to be responsible for the high Ca2+selectivity of channels formed by TRPV5 [3]. 

For all other members of the TRP family it still has to be shown whether the presumptive pore loop or other protein domains actually line the ion conducting pathway of the channel. Based on the results showing that expression of most TRPC channels yields currents carried by Na+and Ca2+, and that expression of TRPM4 and TRPM7 channels yields currents carried by Na+ but not by Ca2+(TRPM4) or even currents carried by Mg2+or Ca2+(TRPM7), it seems likely that the pore structures of these channel proteins vary considerably. 

Grunewald M., Menaker D., and Kanner B. I. (2002). Cysteine-scanning mutagenesis reveals a conformationally sensitive reentrant pore-loop in the glutamate transporter GLT-1. J. Biol. Chem. 277 26074-26080. 

Fig. 4. A homology model of the channel domain of an NMDA receptor (Chohan et al, 2000) based on the structure of the KcsA channel (Doyle et al, 1998). (A) The side view of the channel is shown with only the Ml, M2, and M3 regions and each of the four subunits in a different color. Note that M2 is a reentrant pore loop that enters the pore from the cytoplasmic face of the membrane. (B) A view of the channel from the extracellular side of the membrane is shown. Both selectivity and gating is controlled at least partially by the M2 region. (See Color Insert.)...

Potassium channels are the most widely distributed type of ion channel and are found in virtually all living organisms. Potassium channels have a tetrameric structure in which four identical protein subunits associate to form a fourfold symmetric (C4) complex arranged around a central ion-conducting pore (a homotetramer). Alternatively, four related but not identical protein subunits may associate to form a heterotetramer with pseudo C4 symmetry. All potassium-channel subunits have a distinctive pore-loop structure that lines the top of the pore and is responsible for potassium-selective permeability. 

FIGURE 9.3 One of the first pictures of a tetrameric K" " channel with a selectivity filter made of pore loops. A linear representation of a Shaker K" channel subunit on top shows shaded hydrophobic segments SI—S6 and a region designated the pore loop. A partial amino acid sequence from the Shaker K" channel pore loop highlights amino acids shown to interact with extracellular scorpion toxins ( ), intracellular tetraethylammonium (f), and ions (+). The pore loop was proposed to reach into the membrane (middle) and form a selectivity filter at the centre of four subunits (bottom). (From MacKinnon, 2004. Reproduced with permission from John Wiley Sons.)... 

We saw earlier how the 3-D structure of a two transmembrane bacterial K" " channel, KcsA, analogous to the inwardly rectifying K+ channels, reveals an inverted tepee arrangement around a central pore, with the narrow outer mouth of the pore formed by the pore loop (Figure 9.7). Information on how the pore might be opened comes... 

Structurally, all K" " channels form a pore-loop and can have a 2TM, 6TM, 7TM, or STM segment architecture (Figure 16.4). Functionally, the channels form four major families ... 

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