Carboxy-terminus

Parkin is a ubiquitin ligase encoded by a gene affected in autosomal recessive juvenile parkinsonism (AR-JP). This gene is located on chromosome 6 and encodes a protein of 465 amino acid residues with moderate similarity to ubiquitin at the amino terminus and a RING-finger motif at the carboxy terminus. 

In addition to the membrane-inserted core domain of Kv channels, their cytoplasmic domains have important roles for Kv-channel function [5]. Many of these functions are related to subunits assembly, channel trafficking to and from the plasma membrane, and interactions with cytoskeletal components (Fig. la). A tetramerization (T) domain for subunit assembly has been well defined in Shaker-channels, where it is localized in the amino-terminus. Other Kv-channels (e.g., eag, HERG, KvLQTl) may have comparable domains within the cytoplasmic carboxy-terminus. ER retention and retrieval signals have been found... 

Trypsin The carboxy terminus sides of lysine (except when proline is attached) and arginine... 

Chymotrypsin The carboxy terminus sides of phenylalanine, tryptophan and tyramine... 

Cyanogen bromide The carboxy terminus side of methionine... 

The proteolytic digestion of j6-lactoglobulin was carried out with trypsin which, as indicated in Table 5.4 above, is expected to cleave the polypeptide backbone at the carboxy-terminus side of lysine (K) and arginine (R). On this basis, and from the known sequence of the protein, nineteen peptide fragments would be expected, as shown in Table 5.7. Only 13 components were detected after HPLC separation and, of these, ten were chosen for further study, as shown in Table 5.8. 

Other interesting examples of proteases that exhibit promiscuous behavior are proline dipeptidase from Alteromonas sp. JD6.5, whose original activity is to cleave a dipeptide bond with a prolyl residue at the carboxy terminus [121, 122] and aminopeptidase P (AMPP) from E. coli, which is a prohne-specific peptidase that catalyzes the hydrolysis of N-terminal peptide bonds containing a proline residue [123, 124]. Both enzymes exhibit phosphotriesterase activity. This means that they are capable of catalyzing the reaction that does not exist in nature. It is of particular importance, since they can hydrolyze unnatural substrates - triesters of phosphoric acid and diesters of phosphonic acids - such as organophosphorus pesticides or organophosphoms warfare agents (Scheme 5.25) [125]. 

CSS Churg-Strauss syndrome CT Computed tomography CTAP-III Connective tissueactivating peptide CTD Connective tissue diseases C terminus Carboxy terminus of peptide... 

Fig. 1. Diagrammatic representation of CCR7 showing the arrangement of the transmembrane domains, the intra- and extracellular loops, and the amino-terminus and carboxy-terminus.

A further importance of cysteines lies in the palmitoylation of chemokine receptors. Many chemokine receptors have cysteine residues in their carboxy-terminal regions. In other GPCRs, these have been implicated in palmitoylation and in the anchoring of the carboxy-terminus to the plasma membrane. This effectively generates a fourth intracellular loop in the receptors. Studies on CCR5 have identified a three-cysteine cluster in the carboxy-terminus that is... 

Kawai T, Choi U, Whiting-Theobald NL, et al. Enhanced function with decreased internalization of carboxy-terminus truncated CXCR4 responsible for WHIM syndrome. Exp Hematol 2005 33 460-468. 

Figure 7.5. Peptide array construction by SPOT-synthesis. fl-alanine groups (b-A) interact with the cellulose filter that serves as a planar support. Peptide synthesis then proceeds using Fmoc chemistries using the fl-alanine group as a starting point. The peptide is attached to the filter via its carboxy-terminus. In this case, lysine is added at the second position and various amino acids are present at the amino terminus of the peptide.

It was determined that the minimal peptide sequence required to stimulate pheromone biosynthesis was the C-terminal 5 amino acids, FXPRLamide, and that the carboxy terminus needs to be amidated [148,149]. This sequence was also established as the minimal sequence required for myotropic activity in cockroaches [ 150] and induction of embryonic diapause in B. mori [ 151 ]. Crossreactivity of peptides containing the FXPRLamide motif was also established for myotropic, diapause induction, and pheromone biosynthesis [152-154]. Therefore, the common C-terminal FXPRLamide defines this family of peptides. A partial listing of peptides identified to date is shown in Table 1. 

The carboxy terminus of the ft receptor was essential for agonist-induced desensitization [83, 132] since truncation of the receptor prevented desensitization. Like those findings with the k receptor, the enzyme G protein receptor kinase (GRK) appears to be involved in the desensitization process, since blockade of GRK prevented the desensitization process. Wang [132] has proposed that GRK catalyzes the phosphorylation of a series of serine/threonine residues in the C-terminus of the fi receptor to desensitize the receptor. 

After attachment of amino acids to tRNA, the amino acids are assembled beginning with the amino terminus and proceeding in the direction of the carboxy terminus. The ribosome is the machinery that translates the mRNA into protein. The ribosome is a very complex protein that contains ribosomal RNA as a functional and structural component. The ribosome assembles around the mRNA, and the cap and other signals allow alignment of the mRNA into the correct position. The initial assembly of the mRNA into the ribosome requires association of the small ribosomal subunit with an initiator tRNA (Met or fMet). Small is a misstatement, because the small ribosomal subunit is a large, complex assembly of numerous smaller proteins—it s just smaller than the... 

Figure 8.3 Schematic representation of the general domain structure of a STAT protein. A conserved ( C or con ) domain is located at the N-terminus, followed by the DNA-binding domain (D). Y represents a short se-guence that contains the tyrosine residue phosphorylated by the Janus kinase. The carboxy terminus domain (Tr) represents a transcriptional activation domain...

Several active forms of the synthetase seem to be inducible in human cells 40 kDa and 46 kDa variants have been identified that differ only in their carboxy terminus ends. They are produced as a result of differential splicing of mRNA transcribed from a single gene found on chromosome 11. A larger 85-100 kDa form of the enzyme has been detected, which may represent a heterodimer composed of the 40 and 46 kDa variants. 

Multiple genes exist for both a- and (3-tubulins. Tubulin isotypes differ primarily at the carboxy-terminus, the region where most post-translational modifications and MAP interactions occur. While most a- and (3-tubulin isotypes are expressed in all tissues, some are expressed preferentially in different tissues. For example, class III and IVa (3-tubulins are neuron-specific (reviewed in [3,14]). It is not known if such examples of tissue-specific... 

Soluble forms of guanylyl cyclase are activated by nitric oxide. These enzymes are homologous to the catalytic domains of the membrane-bound forms of GC. They are considered heterodimers because they appear to exist, under physiological conditions, as complexes of a and P subunits, each with Mr of 70-80 kDa. Both types of soluble GC contain three primary domains an amino-terminus heme domain responsible for binding nitric oxide (NO), a dimerization domain and a carboxy terminus catalytic domain. The aP heterodimer is required for enzyme activity [35]. This can be seen as similar to the situation for AC, which contains two catalytic entities within a single polypeptide chain (Fig. 21-5). 

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