Introduction of Protein Acetylation
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Protein acetylation commonly has two different forms. In humans, almost (80%-90%) proteins become co-translationally acetylated at their Nα-termini of the nascent polypeptide chains. Another type is typically acetylated on lysine residues.
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Introduction of Protein Acetylation
- 1. Brief Introduction of Protein Acetylation Creative Proteomics Presentation
- 2. Protein Acetylation Acetylation refers to a reaction that introduces an acetyl functional group into a chemical compound, in which the hydrogen atom of a hydroxyl group is replaced by an acetyl group (CH3 CO) to yield a specific ester, the acetate. N-terminal acetylation Lysine acetylation
- 3. N-terminal acetylation N-terminal (Nt) acetylation are catalyzed by N-terminal- acetyltransferases (NATs) and is found to be irreversible so far. Drazic, Adrian, et al. "The world of protein acetylation." Biochimica et Biophysica Acta (BBA)-Proteins and Proteomics1864.10 (2016): 1372-1401. NATs, mono- or multisubunit enzymes consisting of a catalytic subunit and up to two auxiliary subunits, can transfer an acetyl group from acetyl-coenzyme A (Ac- CoA) to the α-amino group of the first amino acid residue of the protein. In humans, there are six NATs have been found so far, including NatA, NatB, NatC, NatD, NatE and NatF
- 4. N-terminal acetylation Drazic, Adrian, et al. "The world of protein acetylation." Biochimica et Biophysica Acta (BBA)-Proteins and Proteomics1864.10 (2016): 1372-1401. Nt acetylation plays different roles in molecular effects.
- 5. N-terminal acetylation has many functions in physiology. N-terminal acetylation NATs is essential for normal development, bone and blood vessel development. N-terminal acetylation can regulate blood pressure, proteasome localization, hormone, as well as organelle structure and function. In human disease, it relate to neurodegenerative diseases (such as Alzheimer's disease, Parkinson's disease and Lewy body dementia) and cancer (like lung cancer, breast cancer, colorectal cancer).
- 6. Lysine Acetylation Unlike Nt acetylation, lysine acetylation is reversible. The acetylation is catalyzed by lysine acetyltransferases (KATs) and the deacetylation of lysine residues is catalyzed by lysine deacetylases (KDACs). Acetylated lysine residues were first discovered in histones regulating gene transcription. This is the reason why the enzymes catalyzing lysine (K) acetyltransferases were termed histone acetyltransferases (HATs) and lysine deacetylases were termed histone deacetylases (HDACs). But lysine acetylation is not limited to histones.
- 7. Lysine acetylation: KATs It is reported that 17-22 genes KATs have been identified in human genome (The exact number of KATs is controversial), which can be classified into three different families, including GCN5 (general control non- derepressible 5)-related acetyltransferase (GNAT) family, the MYST family, and p300/CBP (CREB-binding protein) family. The known substrates of KAT complexes not only include histone proteins, but some different transcription factors, transcriptional co-regulators, and some proteins of specific cellular signaling pathways like p53, β- catenin, NF-κB, MyoD or Rb. Biancotto, Chiara, Gianmaria Frigè, and Saverio Minucci. "Histone modification therapy of cancer." Advances in genetics. Vol. 70. Academic Press, 2010. 341-386.
- 8. Lysine acetylation: KDACs Schneider, Günter, et al. "Targeting histone deacetylases in pancreatic ductal adenocarcinoma." Journal of cellular and molecular medicine 14.6a (2010): 1255-1263. The KDAC family has phylogenetically been divided into four classes according to their homology in the catalytic domain. Classes I, II and IV bear homology to each other as well as orthology to the same Saccharomyces cerevisiae proteins (Rpd3 and Hda1), which catalyze deacetylation in a Zn2+ dependent manner. While Class III, Sirtuins contains seven members from SIRT1 to SIRT7 that bears homology to the Saccharomyces cerevisiae protein. In contrast to the other three, Sirtuins are nicotinamide–adenine– dinucleotide (NAD+) dependent deacetylases and ADP-ribosyltransferases.
- 9. Lysine acetylation The histone proteins are associated with a tight regulation of essential all types of DNA- templated processes, such as transcription, replication, recombination, repair, translation and formation of specialized chromatin structures. Therefore, protein lysine acetylation affect a range of cellular signaling pathways as well as metabolism, stress responses, apoptosis and membrane trafficking. Together with DNA, histone proteins form the so called nucleosomes. One nucleosome consists of about 150–200 bps of DNA. Histone acetylation can determine the histone assembling as well as the folding and compactness of the DNA-histone interaction and therefore presenting a switch between permissive and repressive chromatin structure.
- 10. Lysine acetylation With the development of mass spectrometry (MS), it has been an important tool for the identification and quantification of lysine acetylation. Zhang, Kai, Shanshan Tian, and Enguo Fan. "Protein lysine acetylation analysis: current MS-based proteomic technologies." Analyst 138.6 (2013): 1628-1636.
- 11. Professional Platforms Creative Proteomics has established a highly sensitive HPLC-MS/MS platform that can analyze acetylation in multiple samples and in both eukaryotic and prokaryotic organisms. In addition, we have optimized our protocol to enable more fast and sensitive site mapping service for acetylation analysis. Our Service
- 12. THANK YOU ! Web: www.creative-proteomics.com Email: info@creative-proteomics.com
Notes de l'éditeur
- Hello, welcome to watch Creative Proteomics’Video. Today, we are going to briefly introduce Protein Acetylation，one of the post translational midifications.
- Acetylation refers to a reaction that introduces an acetyl functional group into a chemical compound, in which the hydrogen atom of a hydroxyl group is replaced by an acetyl group to yield a specific ester, the acetate. Protein acetylation commonly has two different forms. In humans, almost proteins become co-translationally acetylated at their N-termini of the nascent polypeptide chains. Another type is typically acetylated on lysine residues.
- N-terminal (Nt) acetylation are catalyzed by N-terminal-acetyltransferases (NATs) and is found to be irreversible so far. NATs, mono- or multisubunit enzymes consisting of a catalytic subunit and up to two auxiliary subunits, can transfer an acetyl group from acetyl-coenzyme A (Ac-CoA) to the α-amino group of the first amino acid residue of the protein. In NATs, the major auxiliary subunit modulates the activity and substrate specificity of the catalytic subunit. Different NATs are responsible for the Nt acetylation. In humans, there are six NATs have been found so far, including NatA, NatB, NatC, NatD, NatE and NatF. In addition to the difference in subunit composition, the various NATs vary in their substrate specificities.
- Nt acetylation plays different roles in molecular effects. Firstly, Nt-acetylation determines the subcellular localization for certain proteins. For example, Arl3 and Grh1, two Golgi-associated proteins, cannot associate with the Golgi apparatus when missing the Nt-acetyl group. Secondly, it is reported that Nt-acetylation restrains proteins in the cytosol and inhibits a post-translational translocation migration to the endoplasmic reticulum (ER) and the secretory pathway. In addition, Nt acetylation can alter the properties of the N-terminus to make protein-protein interactions become modulated. It was shown for several proteins that the affinity to their binding partners increased after being Nt-acetylated. For example, The E2 ubiquitin-conjugating enzyme Ubc12 undergoes Nt-acetylation by NatC enabling an increased affinity towards its interaction partner, the E3 ubiquitin ligase Dcn1. Moreover, Nt-acetylation controls protein quality and lifetime, and regulates the protein stoichiometry by the N-end rule pathway.
- N-terminal acetylation has many functions in physiology. NATs is essential for normal development, bone and blood vessel development. N-terminal acetylation can regulate blood pressure, proteasome localization, hormone, as well as organelle structure and function. In human disease, it related to neurodegenerative diseases (such as Alzheimer's disease, Parkinson's disease and Lewy body dementia) and cancer (like lung cancer, breast cancer, colorectal cancer).
- Unlike N-terminal acetylation, lysine acetylation is reversible. The acetylation is catalyzed by lysine acetyltransferases, and the deacetylation of lysine residues is catalyzed by Lysine deacetylases. Acetylated lysine residues were first discovered in histones regulating gene transcription. But it is not limited to histones. Acetylated lysine residues were first discovered in histones regulating gene transcription, This is the reason why the enzymes catalyzing lysine (K) acetyltransferases were termed histone acetyltransferases (HATs) and lysine deacetylases were termed histone deacetylases (HDACs). But lysine acetylation is not limited to histones.
- It is reported that 17-22 genes lysine acetyltransferases have been identified in human genome, which can be classified into three different families, including GNAT family, the MYST family, and p300 CBP family. The known substrates of lysine acetyltransferases complexes not only include histone proteins, but some different transcription factors, transcriptional co-regulators, and some proteins of specific cellular signaling pathways like p53 and β-catenin.
- The lysine deacetylases family has phylogenetically been divided into four classes according to their homology in the catalytic domain. Classes I, II and IV bear homology to each other as well as orthology to the same Saccharomyces cerevisiae proteins (Rpd3 and Hda1), which catalyze deacetylation in a Zn2+-dependent manner. While Class III, Sirtuins contains seven members from SIRT1 to SIRT7) that bears homology to the Saccharomyces cerevisiae protein. In contrast to the other three, Sirtuins are nicotinamide–adenine–dinucleotide (NAD+) dependent deacetylases and ADP-ribosyltransferases.
- Together with DNA, histone proteins form the so called nucleosomes. One nucleosome consists of about 150–200 bps of DNA. histone acetylation can determine the histone assembling as well as the folding and compactness of the DNA-histone interaction and therefore presenting a switch between permissive and repressive chromatin structure. The histone proteins are associated with a tight regulation of essential all types of DNA-templated processes as transcription, replication, recombination, repair, translation and formation of specialized chromatin structures. Therefore, protein lysine acetylation affect a range of cellular signaling pathways as well as metabolism, stress responses, apoptosis and membrane trafficking.
- With the development of mass spectrometry (MS), it has been an important tool for the identification and quantification of lysine acetylation. To analysis histone lysine acetylation,there are several steps, including cell lysate, histone extraction, histone separation, mass spectrometry, and data analysis. The steps for analysis for protein lysine acetylation from whole cell include cell lysate, protein separation, enrichment of lysine acetylation peptides, separation of lysine acetylation peptides, mass spectrometry, and data analysis.
- Creative Proteomics has established a highly sensitive HPLC-MS/MS platform that can analyze acetylation in multiple samples and in both eukaryotic and prokaryotic organisms. In addition, we have optimized our protocol to enable more fast and sensitive site mapping service for acetylation analysis.
- Thanks for watching our video. At creative proteomics, we provide the most reliable serivices. If you have any questions or specific requirements. Please do not hesitate to contact us. We are very glad to cooperate with you.