Domains carboxyl terminal repeat

Figure 7.16. Sequence Alignment of Internal Repeats. (A) An alignment of the sequences of the two repeats of the TATA-hox-binding protein. The amino-terminal repeat is shown in green and the carboxyl-terminal repeat in blue. (B) Structure of the TATA-hox-binding protein. The amino-terminal domain is shown in green and the carboxyl-terminal domain in blue.

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. 

HSF3, identified in chicken, is induced by c-Myb in the absence of cellular stress (Nakai and Morimoto, 1993 Kanei-Ishii et al., 1997). Another isoform of HSF found in human cells, HSF4, possesses transcription represser properties in vivo (Frejtag et al., 2001). Comparisons of HSF protein structure in these organisms indicate the presence of conserved DNA binding domain and three hydrophobic heptad repeats that constitute the trimerization domain. These domains are located within the amino-terminal region of the protein. The stress-responsive transcriptional activation domain is located in the carboxyl-terminal region of the molecule. 

S, and 28S ribosomal RNA (Section 29.3.1). The other ribosomal RNA molecule (5S rRNA, Section 29.3.1) and all the transfer RNA molecules (Section 29.1.2) are synthesized by RNA polymerase III, which is located in the nucleoplasm rather than in nucleoli. RNA polymerase II, which also is located in the nucleoplasm, synthesizes the precursors of messenger RNA as well as several small RNA molecules, such as those of the splicing apparatus (Section 28.3.5). Although all eukaryotic RNA polymerases are homologous to one another and to prokaryotic RNA polymerase, RNA polymerase II contains a unique carboxyl-terminal domain on the 220-kd subunit this domain is unusual because it contains multiple repeats of a YSPTSPS consensus sequence. The activities of RNA polymerase II are regulated by phosphorylation on the serine and threonine residues of the carboxyl-terminal domain. Another major distinction among the polymerases lies in their responses to the toxin a -amanitin, a cyclic octapeptide that contains several modified... 

TBP bound to the TATA box is the heart of the initiation complex (see Figure 28.19). The surface of the TBP saddle provides docking sites for the binding of other components (Figure 28.21). Additional transcription factors assemble on this nucleus in a defined sequence. TFIIA is recruited, followed by TFIIB and then TFIIF—an ATP-dependent helicase that initially separates the DNA duplex for the polymerase. Finally, RNA polymerase II and then TFIIE join the other factors to form a complex called the basal transcription apparatus. Sometime in the formation of this complex, the carboxyl-terminal domain of the polymerase is phosphorylated on the serine and threonine residues, a process required for successful initiation. The importance of the carboxyl-terminal domain is highlighted by the finding that yeast containing mutant polymerase II with fewer than 10 repeats is not viable. Most of the factors are released before the polymerase leaves the promoter and can then participate in another round of initiation. 

Although all eukaryotic RNA polymerases are homologous to one another and to prokaryotic RNA polymerase, RNA polymerase II contains a unique carboxyl-terminal domain on the 220-kd subunit called the CTD this domain is unusual because it contains multiple repeats of a YSPTSPS consensus sequence. The activity of RNA polymerase II is regulated by phosphorylation mainly on the serine residues of the carboxyl-terminal domain. Another major distinction among the polymerases lies in their responses to the toxin a-amanitin, a cyclic octapeptide that contains several modified amino acids. 

The carboxyl end of the largest subunit of RNA polymerase II (RPBI) contains a stretch of seven amino acids that Is nearly precisely repeated multiple times. Neither RNA polymerase I nor III contains these repeating units. This hep-tapeptlde repeat, with a consensus sequence of Tyr-Ser-Pro-Thr-Ser-Pro-Ser, Is known as the carboxyl-terminal domain (CTD). Yeast RNA polymerase II contains 26 or more repeats, the mammalian enzyme has 52 repeats, and an Intermediate number of repeats occur In RNA polymerase II from nearly all other eukaryotes. The CTD Is critical for viability, and at least 10 copies of the repeat must be present for yeast to survive. 

Thiolated polymers, also termed thiomers, are conventional mucoadhesive polymers chemically modified to contain a cysteine residue in the polymer chain and thus establish covalent disulfide bonds with mucin." They can be manufactured to be either cationic (mostly thiolated chitosans) or anionic (carboxylic acid-containing polymers) however, their mucoadhesive extent will mostly be determined by their capacity to covalently bind to mucin. The polypeptide backbone of mucin can be divided into three major subunits tandem repeat array, carboxyl-, and amino-terminal domains. While the amino-terminal domain contains some of the cysteine residues, the carboxyl-terminal domain contains more than 10% of the cysteine residues. These cysteine-rich regions are responsible for forming the large mucin oligomers and ultimately, the groups that allow for the covalent mucoadhesive bond formation with oral mucosal systems." ... 

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