Heterotrimer

The G-proteins are heterotrimers made of three families of subunits, a, P, and y, which can interact specifically with discrete regions on G-protein-coupled receptors. This includes most receptors for neurotransmitters and polypeptide hormones (see Neuroregulators). G-protein-coupled receptors also embrace the odorant receptor family and the rhodopsin-linked visual cascade. 

FIGURE 15.21 Hormone (H) binding to its receptor (R) creates a hormone receptor complex (H R) that catalyzes GDP-GTP exchange on the o -subunit of the heterotrimer G protein (G ), replacing GDP with GTP. The G -subunit with GTP bound dissociates from the /37-subunits and binds to adenylyl cyclase (AC). AC becomes active upon association with G GTP and catalyzes the formation of cAMP from ATP. With time, the intrinsic GTPase activity of the G -subunit hydrolyzes the bound GTP, forming GDP this leads to dissociation of G GDP from AC, reassociation of G with the /Sy subunits, and cessation of AC activity. AC and the hormone receptor H are integral plasma membrane proteins G and G are membrane-anchored proteins. 

It should be noted that fast inactivation of receptor signaling not only involves the desensitization of the receptor but also the components of the downstream signaling cascade. The deactivation of active Ga subunits is controlled by the intramolecular hydrolysis of bound GTP, allowing it to reform the inactive heterotrimer. Termination of G protein-mediated signaling in vivo is 10- to 100-fold faster than the in vitro rate of GTP hydrolysis by Ga subunits, suggesting... 

G-protein activation has a cyclical nature. The a subunit can hydrolyze the GTP that is bound to it, thereby allowing the heterotrimer to reform. The lifetime of individual aGTP subunits will vary (cf. the lifetimes of open ion channels). 

Adjobo-Hermans, M. J., Goedhart, J. and Gadella, T. W., Jr. (2006). Plant G protein heterotrimers require dual lipidation motifs of G(alpha) and G(gamma) and do not dissociate upon activation. J. Cell Sci. 119, 5087-97. 

Nikolaev, V. O., Hoffmann, C., Bunemann, M., Lohse, M. J. and Vilardaga, J. P. (2006). Molecular basis of partial agonism at the neurotransmitter alpha2A-adrenergic receptor and Gi-protein heterotrimer. J. Biol. Chem. 281, 24506-11. 

Each G protein is a heterotrimer composed of single a, P and y subunits 336... 

There are two similar a chains in type Vlll collagen, al(Vlll) and a2(VllI). Two homotrimeric subtypes, [q 1(VIII)]3 and [o 2(VIII)]3, are suggested to be the major molecular species,but a heterotrimer can also exist. Stephan et analyzed the purified type Vlll collagen by atomic force microscopy and electron microscopy. They confirmed the tetrahedron model from biochemical analysis and ultrastructural studies. 

All of the 12 fibril-forming a chains share a long uninterrupted collagenous domain flanked by N- and C-terminal NC propeptides. The a chains assemble into at least 12 type-specific protomers, characterized as homo- and heterotrimers. The chains of fibrillar collagens associate first through a series of noncovalent interactions between the C-terminal NC domains (NCI), which provide correct alignment and registration for... 

The al and a2 chains of type VI collagen are similar in size and contain one N-terminal NC domain and a C-terminal NC domain with two subdomains. Cl and C2. In contrast, the a3 chain is much longer, and the N-terminal NC domain contains 10 subdomains, Nl-NlO, and 5 C-terminal NC subdomains, Cl-C5. The protomer is an ala2a3 heterotrimer. Deletion studies have demonstrated that whereas the C5 subdomain of the a3 chain is required for the extracellular microfibril formation, the Cl subdomain, in all chains, is sufficient for chain recognition and protomer assembly... 

A second example of a membrane-bound arsenate reductase was isolated from Sulfurospirillum barnesii and was determined to be a aiPiyi-heterotrimic enzyme complex (Newman et al. 1998). The enzyme has a composite molecular mass of 100kDa, and a-, P-, and y-subunits have masses of 65, 31, and 22, respectively. This enzyme couples the reduction of As(V) to As(III) by oxidation of methyl viologen, with an apparent Kra of 0.2 mM. Preliminary compositional analysis suggests that iron-sulfur and molybdenum prosthetic groups are present. Associated with the membrane of S. barnesii is a h-type cytochrome, and the arsenate reductase is proposed to be linked to the electron-transport system of the plasma membrane. 

Figure 8.1. Schematic showing the hydrolysis of the type I tropocollagen (TC) heterotrimer [ol1(I)]20t2(I), by tissue (right) and bacterial (left) collagenases.

G proteins transfer signals from 7-helix receptors to effector proteins (see above). G protein are heterotrimers consisting of three different types of subunit (a, 3, and y see p.224). The a-subunit can bind GDP or GTP (hence the name G protein ) and has GTPase activity. Receptor-coupled G proteins are related to other GTP-binding proteins such as Ras (see pp. 388, 398) and EF-Tu (see p. 252). 

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