Protein Modifications

SUMOylation. Figure 1 SUMOylation is a reversible and regulated process. Target protein modification by SUMO can be initiated and terminated by different cues. Sumoylation leads to changes in the behavior of the modified protein, for example, different cellular localization, enhanced/reduced activity, or increased stability. These changes are due to alterations either in protein interactions or protein folding. 

Protein modification by the covalent attachment of ubiquitin chains serves as a signal to mark proteins for the degradation by a multicatalytic proteinase complex called the proteasome. Thus the ubiquitin proteasome system (UPS) controls the stability of proteins in a... 

The reactions described so far do not require the involvement of the apo-B protein, neither would they necessarily result in a significant amount of protein modification. However, the peroxyl radical can attack the fatty acid to which it is attached to cause scission of the chain with the concomitant formation of aldehydes such as malondialdehyde and 4-hydroxynonenal (Esterbauer et al., 1991). Indeed, complex mixtures of aldehydes have been detected during the oxidation of LDL and it is clear that they are capable of reacting with lysine residues on the surface of the apo-B molecule to convert the molecule to a ligand for the scavenger receptor (Haberland etal., 1984 Steinbrecher et al., 1989). In addition, the lipid-derived radical may react directly with the protein to cause fragmentation and modification of amino acids. 

Figure 3.2 Proposed mechanisms of protein modification through carbonyi interactions involving monosaccharides [from Brownlee et af. (1988) and Wolff and Dean (1987)].

Wolff, S. and Dean, R, (1987). Glucose autoxidation and protein modification. Biochem. J. 245, 243-250. 

Augusteyn, R.C. (1981). Protein modification in cataract possible oxidative mechanisms. In Mechanisms of Cataract Formation in the Human Lens (ed. G. Duncan) pp. 71-115, Academic Press, London. 

We are attempting to understand the biological significance of the large variations in frequency of putative LDRs, whether between different types of bacteria or archaea, or between pro- and eukaryota. We have carefully studied the literature of more than 90 example proteins selected from our disordered protein databases and found reports on the functions of most of the disordered regions (Dunker et al., 2002). The observed functions and the number of examples in each functional class are given in Table VI. As indicated, four major functional classes were found molecular recognition, molecular assembly or disassembly, protein modification, and entropic chains. 

Protein modification 36 Variable Acetylation, fatty acylation, glycosylation, methylation, phosphorylation, ADP-ribosylation, ubiquitination, proteolytic digestion... 

Meng, F., Forbes, A.J., Miller, L.M., Kelleher, N.L. (2005). Detection and localization of protein modifications by highresolutiontandemmass spectrometry. Mass Spectrom. Rev. 24,126-134. 

LaVoie, M.J., Hastings, T.G. Dopamine quinone formation and protein modification associated with the striatal neurotoxicity of methamphetamine evidence against a role for extracellular dopamine. J. Neurosci. 19 1484, 1999. 

The key feature of the PDA technology is that a far wider biological diversity can be screened computationally than it is possible with exclusively experimental methods. The in silico approach provides unique and original gene modifications whilst maintaining the precise control over the extent and nature of protein modifications. The novel sequences... 

Richardson FC et al. Dose responses in rat hepatic protein modification and expression following exposure to the rat he-patocarcinogen methapyrilene. Carcinogenesis 1994 15 325-329. 

Smith, J. J., Conrad, D. W., Cuneo, M. J. and Hellinga, H. W. (2005). Orthogonal site-specific protein modification by engineering reversible thiol protection mechanisms. Protein Sci. 14, 64-73. 

Tanaka, T., Yamamoto, T., Tsukiji, S. and Nagamune, T. (2008). Site-specific protein modification on living cells catalyzed by sortase. Chembiochem 9, 802-7. 

Fowles LF, Beck E, Worrall S, et al.The formation and stability of imidazolidinone adducts from acetaldehyde and model peptides. A kinetic study with implications for protein modification in alcohol abuse. Biochem. Pharmacol. 1996 51 1259-1267. 

The goal of most protein modification or conjugation procedures is to create a stable product with good retention of the native state and activity. Ideally, any derivatization should result in a protein that performs exactly as it would in its unmodified form, but with the added functionality imparted by whatever is conjugated to it. Thus, an antibody molecule tagged with a fluorophore should retain its ability to bind to antigen and also have the added functionality of fluorescence. 

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