Cytoplasmic loop

Mutations in another region, the second cytoplasmic loop between M2 and M3 in Ca-ATPase of sarcoplasmic reticulum (Thr ->Ala, Gly -t Ala, and Glu Gln) also result in a complete loss of Ca-transport and Ca-ATPase activity associated with a dramatic reduction in the rate of phosphoenzyme turnover [96]. These mutations do not affect the affinity of the enzyme for Pj and therefore resemble the Pro mutants [123] in that they affect only the E1P-E2P conformational change and not the affinities for ATP, Ca or Pj. 

FIGURE 3.1 Schematic representation of the transmembrane topology of the 4TM receptor family. Only TM2 show an a-helical structure in electron microscopic studies the remaining TM regions may fold in (5-sheet structures. Both the N-terminus (indicated by NH2) and the C-terminus are located extracellularly. The cytoplasmic loops between TM3 and TM4 are variable in size and contain putative phosphorylation sites. 

Fishbum C., Belleli D., David C., Cannon S., Fuchs S. A novel short isoform of the D3 dopamine receptor generated by alternative splicing in the third cytoplasmic loop. J. Biol. Chem. 268 5872, 1993. 

Elliott, C., Muller, J., Miklis, M., Bhat, R. A., Schulze-Lefert, P. and Panstruga, R. (2005). Conserved extracellular cysteine residues and cytoplasmic loop-loop interplay are required for functionality of the heptahe-lical MLO protein. Biochem J. 385, 243-54. 

The cellular and subcellular distributions of a-subunit isoforms provide clues to their different physiological functions. The four isoforms exhibit about 85% sequence identity. The most substantial differences occur in their N-terminal regions and in an 11-residue sequence of the large cytoplasmic loop. When measured in cell cultures, the isoforms differ in their apparent affinities for intracellular Na+ (al < a2 < a3) [21 ] and extracellular K+ (a3 < a2 = al) [22], In adult tissues, al is the major iso form in... 

Chen, N., Ferrer, J. V., Javitch, J. A., and Justice, J. B Jr. (2000) Transport-dependent accessibility of a cytoplasmic loop cysteine in the human dopamine transporter. J. Biol. Chem. 275,1608-1614. 

Most ZIP proteins have eight predicted transmembrane domains (Figure 7.10) and similar predicted topologies with both the N- and C-termini located on the extracytoplasmic face of the membrane with a His-rich domain frequently in the long cytoplasmic loop between transmembrane domains 3 and 4. In contrast, most CDF transporters have six predicted transmembrane domains and a His-rich domain in the loop between domains 4 and 5, but here the N- and C-termini are on the cytoplasmic side of the membrane. 

A key feature of both vertebrate and invertebrate opsin molecules is their ability to interact with a G protein, typically transducin, to initiate phototransduction (Ebrey Koutalos 2001). The third cytoplasmic loop that connects a-hehces V and VI contributes to the G protein binding and activation and is highly conserved amongst the rod and cone opsins (Fig. 1, Table 2). This conservation extends to the P opsin family. However, the third cytoplasmic loop of the VA... 

TABLE 2 Alignment of the third cytoplasmic loop (C3) from representatives of photosensory opsin families and melanopsins... 

The mechanism by which the activated receptor talks to the G-protein is only partially understood. Generally, the switch function of the receptor is considered in terms of allosteric conformational changes of the 7-hehx membrane bimdle (review Bourne, 1997). According to this representation, changes in the structure of the transmembrane bimdle are passed on to the cytoplasmic loops of the receptor. Communication with the a-subunit of the heterotrimeric G-protein takes place via these loops. 

Other effector molecules of the Py-complex are specific subtypes of phospholipase C, and K - and Ca -specific ion charmels. In the case of Ca chaimels, a direct interaction between the Py-complex and cytoplasmic loops of the a-subimit of the ion channel has been demonstrated (De Waard et al., 1997). Regulation of the activity of ion channels is thus a further important role of the Py-complex. 

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