Carboxyl-terminal domain

Figure 5-8. Domain structure. Protein kinases contain two domains. The upper, amino terminal domain binds the phosphoryl donor ATP (light blue). The lower, carboxyl terminal domain is shown binding a synthetic peptide substrate (dark blue).

The hver and many extrahepatic tissues express the LDL (B-lOO, E) receptor. It is so designated because it is specific for apo B-IOO but not B-48, which lacks the carboxyl terminal domain of B-lOO containing the LDL receptor ligand, and it also takes up lipoproteins rich in apo E. This receptor is defective in familial hypercholesterolemia. Approximately 30% of LDL is de-... 

The product of the repressor gene, the 236-amino-acid, 27 IcDa repressor protein, exists as a two-domain molecule in which the amino terminal domain binds to operator DNA and the carboxyl terminal domain promotes the association of one repressor protein with another to form a dimer. A dimer of repressor molecules binds to operator DNA much more tighdy than does the monomeric form (Figure 39-6A to 39-6C). 

Upper panel The hydropathy profile of the entire 69 kD precursor protein is shown. The abscissa is amino acid residues and the ordinate, positive values indicate hydrophilic. The black and hatched rectangles at the bottom of the figure denote the calculated signal sequence and amino-terminal propeptide domains, respectively. The mature and carboxyl-terminal domains are labeled. N-linked core glycosylation consensus sites are depicted by branched structures. 

Kraft K, Olbrich H, Majoul I, Mack M, Proudfoot A, Oppermann M. Characterization of sequence determinants within the carboxyl-terminal domain of chemokine... 

Asano, K., Shalev, A., Phan, L., Nielsen, K., Clayton, J., Valasek, L., Donahue, T. F., and Hinnebusch, A. G. (2001). Multiple roles for the carboxyl terminal domain of eIF5 in translation initiation complex assembly and GTPase activation. EMBOJ. 20, 2326—2337. 

Kolman, C. j., Toth, J., and Gonda, D. K. Identification of a portable determinant of cell cycle function within the carboxyl-terminal domain of the yeast CDC34 (UBC3) ubiquitin conjugating (E2) enzyme. EMBO J. 1992, 3 3, 3081-90. 

The carboxyl-terminal domain of the mammalian enzymes is related to bacterial restriction methyltransferases. Journal of Molecular Biology, 203, 971-983. 

Engelman A, Hickman AB, Craigie R. The core and carboxyl-terminal domains of the integrase protein of human immunodeficiency virus type 1 each contribute to nonspecific DNA binding. J Virol 1994 68 5911-5917. 

Cisek, L.J. Corden, J.L. Purification of protein kinases that phosphorylate the repetitive carboxyl-terminal domain of eukaryotic RNA polymerase IL Methods Enzymol., 200, 301-325 (1991)... 

Payne, J.M. Dahmus, M.E. Partial purification and characterization of two distinct protein kinases that differentially phosphorylate the carboxyl-terminal domain of RNA polymerase subunit Ila. J. Biol. Chem., 268, 80-87 (1993)... 

Patturajan, M. Conrad, N.K. Bregman, D.B. Corden, J.L. Yeast carboxyl-terminal domain kinase I positively and negatively regulates RNA polymerase II carboxyl-terminal domain phosphorylation. J. Biol. Chem., 274, 27823-27828 (1999)... 

Streptomyces tendae Escherichia coli 1 carboxyl-terminal domain Human Homo sapiens)... 

NAD(P)-binding Rossmann-fold domains NAD(P)-binding Rossmann-fold domains Alcohol/glucose dehydrogenases, carboxyl-terminal domain Alcohol dehydrogenase Human Homo sapiens)... 

The amino-terminal domain is on the left the carboxyl-terminal domain on the right, (b) Calmodulin associated with a helical domain (red) of one of the many enzymes it regulates, calmodulin-dependent protein kinase II (PDB ID 1CDL). Notice that the long central a helix visible in (a) has bent back on itself in binding to the helical substrate domain. The central helix is clearly more flexible in solution than in the crystal, (c) Each of the four Ca2+-binding sites occurs in a helix-loop-helix motif called the EF hand, also found in many other Ca2+-binding proteins. 

FIGURE 24-34 Structure of SMC proteins, (a) The five domains of the SMC primary structure. N and C denoted the amino-terminal and carboxyl-terminal domains, respectively, (b) Each polypeptide is folded so that the two coiled-coil domains wrap around each other and the N and C domains come together to form a complete ATP-binding site. Two of these domains are linked at the hinge region to form the dimeric V-shaped molecule, (c) Electron micrograph of SMC proteins from Bacillus subtilis. 

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. 

Another important coactivator consists of 20 or more polypeptides in a protein complex called mediator (Fig. 28-27) the 20 core polypeptides are highly conserved from fungi to humans. Mediator binds tightly to the carboxyl-terminal domain (CTD) of the largest subunit of Pol II. The mediator complex is required for both basal and regulated transcription at promoters used by Pol II, and it also stimulates the phosphorylation of the CTD by TFIIH. Both mediator and TFIID are required at some promoters. As with TFIID, some DNA-binding transactivators interact with one or more components of the mediator complex. Coactivator complexes function at or near the promoter s TATA box. 

Ferguson G, Watterson KR, Palmer TM (2002) Subtype-specific regulation of receptor internalization and recycling by the carboxyl-terminal domains of the human A and rat A3 adenosine receptors consequences for agonist-stimulated translocation of arrestin3. Biochemistry 41(50) 14748-14761... 

Xu, C.B., Verwaerde, C., Gras-Masse, H., Fontaine, J., Bossus, M., Trottein, F., Wolowczuk, I., Tartar, A. and Capron, A. (1993) Schistosoma mansoni 28-kDa glutathione S-transferase and immunity against parasite fecundity and egg viability. Role of the amino- and carboxyl-terminal domains. The journal of Immunology 150, 940-949. 

---