Hetero-oligomerization

Ca2+ Channel Blockers. Figure 1 Most voltage-gated Ca2+ channels exist as a hetero-oligomeric complex of several subunits, a 1 subunits form the Ca2+-selective ion pore and contain the voltage-sensors of the channel. 

ChEs present several amphiphilic and soluble homo-and hetero-oligomeric molecular forms in tissues and body fluids, with different tissue distributions (Fig. 1). 

HVA calcium channels are biochemically hetero-oligomeric complexes of five proteins encoded by four gene families (Fig. 1) The ax subunits of 190-250 kDa contain the voltage-sensor, the selectivity filter, the ion-conducting pore, the binding sites for most calcium... 

The pore-forming oq subunit alone is sufficient to form a functional calcium channel in the cell membrane [8]. However, high-voltage-activated calcium channels are hetero-oligomeric structures that may contain as many as three additional smaller subunits, labeled CX25 (itself a heterodimer), (5, and y. These three subunits associate in an auxiliary... 

The subunit structure of the cytokine receptors is very variable. Amongst the cytokine receptors, there are receptors composed of one polypeptide and receptors made up of two or three different polypeptide chains (Fig. 11.3), which therefore have a hetero-oligomeric structure. The receptors have one transmembrane element per polypeptide chain. The NH2 terminus is located in the extracellular region whilst the CO OH terminus is intracellular. 

It is assumed that the Jak kinases bind to a cytoplasmic section of the receptor, which is in the vicinity of the membrane and contains two conserved sequence elements, Box 1 and Box 2. Binding of the Jak kinases leads to their activation, a process linked to mutual phosphorylation of the Jak kinases (Fig. 11.6). Activation of the Jak kinases may take place in a homodimeric receptor complex or it may also occm in hetero-oligomeric complexes. The circumstances are comphcated in that two (or more) Jak kinases may associate at an activated receptor. Two different Jak kinases are required for signal transduction via interferon receptors (see Fig. 11.8). Furthermore, the different Jak kinases are specific for the corresponding receptors. 

Various members of the Bcl-2 family can interact with another via the BH domains and form hetero-oligomeric complexes in which the different activities neutralize one another. The relationship of proapoptotic and antiapoptotic Bcl-2 family proteins thus helps to determine a cell s susceptibility to apoptosis. 

A model of the GABA receptor-chloride ion channel macromolecular complex. A hetero-oligomeric glycoprotein, the complex... 

Despite the obstacles discussed above, solid-phase syntheses of oligomers do have two significant advantages over solution techniques. First, purifications in solid-phase techniques are easier and faster than in solution and are more likely to be amenable to automation. Second, hetero-oligomerizations are relatively easy to arrange if one component is anchored to a solid phase. Overall, the advantages of solid-phase syntheses of oligomers, as well as other products, can be appreciable for reproducible, reliable, and easily monitored reaction schemes. 

Electron microscopy studies have revealed that, like acetylcholine receptors, the ion channel of the GABA receptor is formed by the pentameric assembly of hetero-oligomeric subunits (129) each subunit has four trans-membrane spanning domains and all five sub-uinits are arranged so that their second transmembrane domains comprise the ion channel wall. Cloning of the subunits from vertebrates has resulted in nearly 20 cDNAs, which have... 

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