Post-translational modification classes

After their synthesis (translation), most proteins go through a maturation process, called post-translational modification that affects their activity. One common post-translational modification of proteins is phosphorylation. Two functional classes of enzymes mediate this reversible process protein kinases add phosphate groups to hydroxyl groups of serine, threonine and tyrosine in their substrate, while protein phosphatases remove phosphate groups. The phosphate-linking... 

Members of this family of molecules may have only one Ig-like domain, as is the case for the myelin protein P0, or, as for most of the family, have many Ig domains. In addition to the subclassification of Ig domains into V-, C- and C2-like domains, Ig family members can be broadly divided into three general classes [8] (a) those that have only Ig-like domains (b) those that have Ig domains and additional domains that resemble regions of the ECM component fibronectin, termed FN-like domains and (c) those that have Ig domains and motifs other than FN-like domains. Moreover, any one Ig family member may have many isoforms, which may differ in the length of the cytoplasmic domain, in their post-translational modifications and whether they are membrane-spanning or glycosylphos-phatidylinositol (GPI)-anchored proteins (see Box 3-1). Also, additional amino acid sequences inserted in the extracellular domain may distinguish isoforms of a particular IgCAM. While it is not known how the majority... 

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... 

The prenyl transferases are a class of enzymes that is involved in post-translational modification of membrane-associated proteins. These enzymes catalyze the transfer of a farnesyl (FTase, EC 2.5.1.58, for structural information see References 55-65) or geranyl-geranyl group (GGTase I, EC 2.5.1.59 GGTase n, EC 2.5.1.60, for structural information... 

The proteins of milk fall into several classes of polypeptide chains. These have been delineated most completely in bovine milk, and a system of nonmenclature has been developed for them (Chapter 3 Eigel et al. 1984). One group, called caseins, consists of four kinds of polypeptides asr, as2-. and 3-, and k- with some genetic variants, post translational modifications, and products of proteolysis. Almost all of the caseins are associated with calcium and phosphate in micelles 20-300 fim in diameter (see Chapter 9). The other milk proteins, called whey proteins, are a diverse group including /3-lactoglobulin, a-lactalbumin, blood serum albumin, and immunoglobulins (Chapter 3). Almost all... 

The processing enzymes can be divided into three classes (a) endopeptidases which cleave the intact precursor into peptide fragments (b) exopeptidases which remove amino acids from the amino or carboxy termini of the peptides and (c) other enzymes involved in the post-translational modification of the peptide. 

The 2D gel approach is ideal for identifying proteins with post-translational modifications, since small changes in protein isoelectric points and size result in dramatic changes in the position of the proteins in the gel. For example, proteins modified by phosphorylation move a considerable distance away from the parent, unmodified protein. Despite the improvements, 2D-PAGE remains technically complicated, and requires that at least triplicate samples be processed for statistical purposes. In addition, some classes of proteins are not detectable, including those that are rare (i.e. low abundance), small (i.e. under 2 kDa), glycosylated, or basic. 

The p53 protein is present in almost all tissues in low concentrations and in a repressed state. Several types of stresses can lead to its accumulation and de-repression by post-translational modifications. These stresses can be broadly divided into three classes (Fig. 14.12) ) ... 

Besides AFl and AF2, 16 other Ascaris FMRFamide-like peptides have been isolated and sequenced (12 sequences are shown in Table 14.2) (194-197 Cowden and Stretton, unpublished). These sequences are unique and not related by post-translational modification or, in most cases, by proteolysis they are also different from FMRFamide-like sequences reported in other organisms, whether obtained from isolated and sequenced peptides, or by deduction from the DNA sequences of genes. It is clear that there is a family of FMRFamide-like peptides in A. suum. They can be divided into several subfamilies related by sequence. Initial experiments on their bioactivity suggest that these may also be functional subfamilies. Measurements of effects on muscle tension, and on input resistance of four types of motoneurons, show that there are at least four classes of biological activity controlled by these peptides AFl and AF2 form one class that causes contraction and the generation of rhythmic activity in muscle (194,197), AF3 and AF4 cause muscle contraction (195), AF5 and AF7 reduce the input resistance of both excitatory and inhibitory motoneurons, and AFl 1 relaxes muscle and increases the input resistance of inhibitory motoneurons (Davis and Stretton, unpublished). 

Advances in the ability to quantitate differences between samples and to detect for an array of post-translational modifications allow for the discoveiy of classes of protein biomarkers that were previously undetectable. Multiplexed LC systems are coupled to MS to analyze affinity-tagged cellular lysates and protein mixtures and someday might replace 2-D gel-based systems. 

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