Carboxyl-terminal tail

An intracellular fibrous system exists of filaments with an axial periodicity of 21 nm and a diameter of 8-10 nm that is intermediate between that of microfilaments (6 nm) and microtubules (23 nm). Four classes of intermediate filaments are found, as indicated in Table 49-13. They are all elongated, fibrous molecules, with a central rod domain, an amino terminal head, and a carboxyl terminal tail. They form a structure like a rope, and the mature filaments are composed of tetramers packed together in a helical manner. They are important structural components of cells, and most are relatively stable components of the cytoskeleton, not undergoing rapid assembly and disassembly and not... 

Mary, S., Gomeza, J., Prezeau, L., Bockaert, J., and Pin, J.-P. (1998) A cluster of basic residues in the carboxyl-terminal tail of the short metabotropic glutamate receptor 1 variants impairs their coupling to phospholipase C. J. Biol. Chem. 273,425 132. 

Scillitani, A., Guarnieri, V., De Geronimo, S., et al. (2004) Blood ionized calcium is associated with clustered polymorphisms in the carboxyl-terminal tail of the calcium-sensing receptor. J. Clin. Endocrinol. Metab. 89, 5634—5638. 

Both mature and nascent forms of ErbB-2 are sensitive to geldanamycin. The drug seems to prevent exit of nascent ErbB-2 from the endoplasmic reticulum (Chavany et al. 1996), and directs the precursor to degradation by the proteasome (Mimnaugh et al. 1996). Sensitivity of ErbB-2 is conferred by the kinase domain of the receptor, but the functionality of the kinase is not necessary, as a kinase-defective mutant of ErbB-2 is also sensitive to geldanamycin (Xu et al. 2001). ErbB-2 is subject to a complex form of degradation, involving the sequential activity of a caspase family protease that cleaves the carboxyl-terminal tail of the receptor from the rest of the molecule (Tikhomirov and Carpenter 2000 Tikhomirov and Carpenter 2001). The cytoplasmic part is ubiquitinated and is subjected to... 

Receptor desensitization may also be mediated by second-messenger feedback. For example, adrenoceptors stimulate cAMP accumulation, which leads to activation of protein kinase A protein kinase A can phosphorylate residues on receptors, resulting in inhibition of receptor function. For the B2 receptor, phosphorylation occurs on serine residues both in the third cytoplasmic loop and in the carboxyl terminal tail of the receptor. Similarly, activation of protein kinase C by Gq-coupled receptors may lead to phosphorylation of this class of G protein-coupled receptors. This second-messenger feedback mechanism has been termed heterologous desensitization because activated protein kinase A or protein kinase C may phosphorylate any structurally similar receptor with the appropriate consensus sites for phosphorylation by these enzymes. 

The largest subunit of Pol II also has an unusual feature, a long carboxyl-terminal tail consisting of many repeats of a consensus heptad amino acid sequence -YSPTSPS-. There are 27 repeats in the yeast enzyme (18 exactly matching the consensus) and 52 (21 exact) in the mouse and human enzymes. This carboxyl-terminal domain (CTD) is separated from the main body of the enzyme by an unstructured linker sequence. The CTD has many important roles in Pol II function, as outlined below. 

The receptors for these hormones are typical seven-transmembrane-domain serpentine peptides (see Chapter 2 Drug Receptors Pharmacodynamics). Each hormone acts as a ligand within a receptor pocket, inducing conformational activating changes in the receptor. The conformational changes in the receptor s intracellular third loop and carboxyl terminal tail activate an adjacent intracellular G protein. The Gm protein is associated with the receptors for GnRH and TRH, G with the dopamine receptor, and Gs protein with the receptors for the other hormones listed above. 

Hayashi MK, Haga T. Palmitoylation of muscarinic acetylcholine receptor m2 subtypes reduction in their ability to activate G proteins by mutation of a putative palmitoylation site, cysteine 457, in the carboxyl-terminal tail. Arch Biochem Biophys 1997 340(2) 376-382. 

Charo, 1. F., Myers, S. J., Herman, A., Franci, C., Connolly, A. J., and Coughlin, S. R. (1994). Molecular cloning and functional expression of two monocyte chemoattractant protein 1 receptors reveals alternative splicing of the carboxyl-terminal tails. Proc. Natl Acad. Sci. USA 91, 2752-2756. 

Lycksell, P. O., Ingemarson, R., Davis, R., Gr%oslund, A., and Thelander, L., 1994, H NMR studies of mouse ribonucleotide reductaseoThe R2 protein carboxyl-terminal tail, essential for subunit interaction, is highly flexible but becomes rigid in the presence of protein Rl. Biochemistry 33 2838n2842. 

Allan GF, Lombardi E, Haynes-Johnson D, Palmer S, Kiddoe M, Kraft P, Campen C, Rybczynski P, Combs DW, Phillips A. Induction of a novel conformation in the progesterone receptor by ZK299 involves a defined region of the carboxyl-terminal tail. Mol. Endocrinol. 1996 10 1206-1213. 

Figure 15.35. Sre Structure. (A) Cellular Sre includes an SH3 domain, an SH2 domain, a protein kinase domain, and a carboxyl-terminal tail that includes a key tyrosine residue. (B) Structure of c-Src in an inactivated form with the key tyrosine residue phosphorylated. The phosphotyrosine residue is bound in the SH2 domain the linker between the SH2 domain and the protein kinase domain is bound by the SH3 domain. These interactions hold the kinase domain in an inactive conformation.

Figure 1. Schematic diagram of the high-density disulfide core and carboxyl-terminal tail containing D-Ser in (B-[D-Ser ]Aga-TK.

The hormone-bound activated receptor must be reset as well to prevent the continuous activation of G proteins. This resetting is accomplished by two processes (Figure 14.10). First, the hormone dissociates, returning the receptor to its initial, unactivated state. The likelihood that the receptor remains in its unbound state depends on the concentration of hormone. Second, the hormone-receptor complex is deactivated by the phosphorylation of serine and threonine residues in the carboxyl-terminal tail. In the example under consideration, adrenergic-receptor kinase (also called G-protein... 

The EGF Receptor Undergoes Phosphorylation of Its Carboxyl-Terminal Tail... 

Immobile trypsin-Sepharose and anti-small subunits IgG-Sepharose can fully interact with the large subunits, but not the small subunits, because the long COOH-terminal extensions of the large subunits run between and above small subunits. The small subunits appear largely covered by the large subunits. Perhaps the carboxyl-terminal tail of the small subunit is slightly exposed to the molecular surface, so the small subunits separated from the large subunit core can enter into solution when immobile holoenzyme is dissociated by 2 M urea. 

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