Post-Translational Modification of Proteins - Essay Example

Post-translational modification of proteins Student’s name Course name and number Name of paper Instructor’s name Date submitted Proteins are of great importance to the human biological system as they play a wide range of functional and structural roles. Proteins are known to for the basic organic basis of various structures of the human system such as the hair, muscles, tendons, cartilage and the skin. All the catalysts that are found in the biochemical transformations and the enzymes too are protein in nature not forgetting hormones such as insulin and the hormones that are responsible for growth. The cytochromes and Hemoglobin which are the substances responsible for the transportation of the electron and oxygen are proteins conjugated. (Olsson A) Post-translational modification of protein is its chemical modification after they have undergone translation. This is one of the processes that are found in the later steps in protein biosynthesis of most proteins. Different amino acids can be involved in proteins during the protein synthesis and after the translational, the post-translational modification of these amino acids make the role of the proteins an extended one since they attach to it other biochemical functional groups. The biochemical groups include acetate, various lipids, phosphate and carbohydrates. (Olsson A) Before the proteins become functional in the different body cells, they undergo chemical modification that is after they have been translated from mRNA. In collective, these modifications are what are referred as post-translational modifications. This post-translation modification of proteins plays an important role. Among some of the important roles of the process is in the generation of heterogeneity in proteins as well as utilizing the proteins that are identical to perform the different cellular functions in the different types of cells. (Donald J. Graves) Post-translational modification of protein This is the process in which there is additional of moiety to a given protein molecule. It is a very common post translational modification of proteins molecules which are involved with the cell membrane formation. In this process, the linking of the amino acids with the monosaccharide units is the center stage for a series of reactions that are enzymatic and they lead to the formation of the glycoprotein, that is the n and the o linked oligosaccharides that are commonly found in the protein entity. A typical glycoprotein has at least 41 bonds which involve 8 amino acids and 13 different monosaccharide units and includes the glycophosphatidylinositol (GPI) and phosphoglycosyl linkages. (Donald J. Graves) The process of Post-translational modification of protein is known to have the control over many biological processes and the help much in trying to understand the cell regulation. Most of the Post-translational modification of proteins is known to take place physiologically. Some of the post-translational modifications of proteins are among them phosphorylation, glycosylation, and acetylation and the process serve many functions. The post-translational modifications is important in the study of diseases in a situation where most genes are found to be involved in diseases like the cancer, heart diseases and diabetes. (Baenziger) When the release of the completed polypeptide chain takes place from the ribosome, there are various covalent modifications that take place after or during the assembly of the polypeptide chain. A lot of the proteins undergo post-translational modifications and these modifications are responsible for altering the chemical and physical properties, conformation, folding, stability, distribution, activity and also the functional properties of the proteins. On the other hand, the modification itself can also be an added group. Some of the biological effects of the protein modifications include the following; phosphorylation for signal transduction, ubiquitination for proteolysis, attachment of fatty acids for membrane anchoring and association, glycosylation for protein half-life, targeting, cell: cell and cell: matrix interactions Like mentioned earlier, the study of the translational modifications of proteins is consequently important in the study of the diseases associated with the heart, cancer, diabetes, and neurodegenerative diseases. The characterizations of the post-translational modifications are challenging but however, they give an invaluable insight into the underlying etiological processes in the cellular functions. (Baenziger) Protein Acetylation Acetylation is a reversible process, in which histone acetyltransferases (HATs) transfer the acetyl moiety from acetyl coenzyme to the amino groups of internal, highly conserved lysine residues. (Kouzarides.) The Modification effect of Protein acetylation plays an important role in the regulation of the transcriptional activity as well as chromatin structure. Many of the co-activators in the transcriptional modification posses’ intrinsic acetylase activity while their counterparts the co-repressors have a great association with deacetylase activity. There are several acetylations so complexes and these include CBP/p300 and PCAF, or also the deacetylation complexes which are Sin3, NuRD, NcoR and SMRT) and they are recruited to DNA-bound transcription factors (TFs) and this is in response to signaling pathways. Other acetylations that are closely associated with this transcriptional activation is among them Histone hyperacetylation by histone acetyltransferases (HATs, and one which is also referred as KATs for lysine acetyltransferases and it is associated with transcriptional activation. (Kouzarides.) The histone acetylation is said to cause stimulation to the transcription by re-modeling chromatic structure of a high order and this will result to the weakening of the histone-DNA interactions and in the end provide binding site for the transcriptional activation complexes that have got proteins which in turn posses bromodomains. The bromodomains bind for the acetylated lysine. The hallmark of silent heterochromatin is the histone hypoacetylation. To site-specific acetylation that are found in a growing number of non-histone proteins is p53 and E2F which have been portrayed as being able to regulate their activity in localization, specific interactions as well as stability/degradation, this enables them to be able to control a variety of cellular processes, which include processes such as transcription, apoptosis, proliferation and differentiation. (Kouzarides.) The crosstalk that exists between acetylation and the other post translational modifications such as phosphorylation and methylation which takes place in the histone and the non-histone proteins is believed to play an important role in the final output signals. Some of the modification will work well when they are in a combinational mode son that they can exert an effect while on the other hand are able to work exclusively well. Acetylation is known to play very important role in the immunity of the human biolo0gical system, the circadian rhythm and also in the memory formation. (Spange S. et al.) Regulation of acetyl-transferase activity The regulation of the enzymatic activity of the acetlylases is done by the proliferation and the differentiation signals (Kouzarides, 2000). This means that the regulatory signal come from phosphorylation or even via the hormonal signaling. A good example which would give evidence that proliferation signals play the function of regulating acetylation is found in the finding that the activity of the HAT of CBP finds its stimulation in the G1-S boundary. This effect is likely mediated by a phoshorylation event which is usually carried out by the cyclin E-CDK complex Kouzarides, 2000). Protein Glycosylation This is acknowledged as one of the major post-translational modifications which have got significant effects on protein conformation, folding, stability, distribution and also activity. Glycosylation has got a diversity of sugar moiety in addition to proteins. These range from simple monosaccharide modifications of nuclear transcription factors to highly complex branched polysaccharide changes of cell surface receptors. Carbohydrates which are (N-linked) aspargine-linked or the (O-linked) serine/threonine oligosaccharides are some of the major components of secreted proteins and many cell surface. (Spiro) The diversity of the oligosaccharide structures are known to result in heterogeneity in the charge and the mass of the glycoprotein. The complex nature of the glycoprotein is found to provide problems for the proteomic analysis. The attachment of sugar residues is one of the most complicated post translational modifications that a protein can undergo. The modification effects of proteins through glycosylation reach beyond the genome in its occurrence and are found to be controlled by various factors that differ among cell types and even species. The organisms that are known to lead to the nature of the carbohydrate units on the glycoprotein is where the glycosylation routes have been identified, these are secreted by the cells is or even becoming the components of its own cytoplasm, membranes. The event that defines this in the biogenesis of the peptide linked oligosaccharides is the nature of the formation of the sugar and the amino acid bond. This is what determines the nature of the carbohydrate units that are to be formed by the cellular enzymatic machinery. (Wells et al) Structures of typical O-linked and N-linked oligosaccharides (a) The O-linked oligosaccharides in glycophorin and many other glycoprotein are linked to the hydroxyl group in serine (Ser) and threonine residues by N-acetylgalactosamine. Collagens contain a characteristic glucose → galactose disaccharide attached to hydroxyl sine (Hyl) residues. (b) The N-linked oligosaccharides found in mammalian serum glycoprotein exhibit various structures, but all contain the five sugars highlighted in purple, are branched, and are linked to the amide nitrogen of asparagines. There are commonly two types of protein glycosylation in which the process is categorized by, these are; N-linked glycosylation It begins with the addition of a 14-sugar precursor to an asparagines amino acid. It contains glucose, mannose and n-acetyl glucosamine molecules. This entity is then transferred to the ER lumen. The oligosaccharyl transferase enzyme attaches the oligosaccharide chain to asparagines that occurs in the tripeptide sequence, Asn-X-Ser or Asn-X-Thr. X can be any amino acid other than Proline. The oligosaccharide attached protein sequence now folds correctly and is now translocated to the Golgi body where the mannose residue is removed. (Wells et al.) O-linked glycosylation Glycosylation begins with an enzyme mediated addition of N-acetyl-galactosamine followed by other carbohydrates to serine or threonine residues. Studies reveal that O linked glycosylation occurs at a later stage in protein processing. Biological Importance of Post-Translational Modification The post translation modifications of proteins which are usually not the gene template based are known to regulate the protein functions through changing the cellular locations of proteins, protein activity and their dynamic interactions with other proteins. Most of the protein modification processes are involved in the signaling pathway which is from the membrane to the nucleus and is in response to the external stimuli. A good example for this is the lingadmediated activation of RTKs and the receptor tyrosine kinases (RTKs) which result to autophosphorylation of both the receptor catalytic domain and also non-catalytic regions. Moreover, besides performing catalytic functions proteins that have been modified by phosphorylation, farnesylation, cysteine, oxidation, acetylation, methylation, myristoylation, and ubiquitination serve as scaffolds for the bringing together many proteins signaling complexes as both transcription and adaptor factors. Conclusion Many of the protein modifications which takes place in the cellular signaling pathways are good in the regulation of the various biological responses when they change the protein activity, binding and localization partners which are often called the post-translamotics. Understanding the relationships that exists between the ptms and physiology gives the complex theory of how the biological process and how it can be regulated with the fine tune having a low error rate. Study on the PTMs will help in a giving a better understanding of the biological process and also the disease states at a molecular level. Works Cited Baenziger, J. U. major step on the road to understandinga unique posttranslational modification and its role in a genetic diseases. 2003. Donald J. Graves, Bruce L. Martin, Jerry H. Wang,. Co- And Post-translational Modification Of Proteins: Chemical Principles And Biological Effects. Oxford University Press , 1994. Kouzarides. Acetylation: a regulatory modification to rival phoshorylation? Vol. 6. EMBO, 2000. Michael W. King. Secreted and Membrane-Associated Proteins. 2 November 2009. 6th January 2010 . Olsson A, Manzl C, Strasser A, Villunger A. Cell Death Differ: How important are post-translational modifications in p53 for selectivity in target-gene transcription and tumour suppression? . 2007. Spange S, Wagner T, Heinzel T, Krämer OH. Acetylation of non-histone proteins modulates cellular signalling at multiple levels. Vols. Cell Biol. 41(1),. Int. J. Biochem, 2008. Spiro, Robert G. "Protein glycosylation: nature, distribution, enzymatic formation, and disease implications of glycopeptide bonds." Glycobiology, Vol. 12 (2002). Wells, L., Whalen, S. A. and Hart, G. W. aregulatory post-translational modification. Biochem. Biophys. 302, 2003. Read More