biology

Protein acetylation

Protein acetylation is a biology topic covered in the lgStudy science library. This page brings together a partial reference excerpt, illustrations, worked examples, real-world applications and a short study plan, so you can understand Protein acetylation rather than just read about it. In short: Protein acetylation (and deacetylation) are acetylation reactions that occur within living cells as drug metabolism, by enzymes in the liver and other organs (e. g., the brain). Pharmaceuticals frequently employ acetylation to enable such esters to cross the blood–brain barrier (and placenta), where they are deacetylated by enzymes (carboxylesterases) in a manner similar to acetylcholine.

Key takeaways

Protein acetylation belongs to biology; place it in that map before memorising details.
Learn the definition first, then one example that makes the definition concrete.
Connect Protein acetylation to a quantity you can measure, compute or draw — that is where exam questions come from.
Reproduce the core statement of Protein acetylation from memory before moving on to harder problems.

Reference excerpt

Protein acetylation (and deacetylation) are acetylation reactions that occur within living cells as drug metabolism, by enzymes in the liver and other organs (e. g., the brain). Pharmaceuticals frequently employ acetylation to enable such esters to cross the blood–brain barrier (and placenta), where they are deacetylated by enzymes (carboxylesterases) in a manner similar to acetylcholine. Examples of acetylated pharmaceuticals are diacetylmorphine (heroin), acetylsalicylic acid (aspirin), THC-O-acetate, and diacerein. Conversely, drugs such as isoniazid are acetylated within the liver during drug metabolism. A drug that depends on such metabolic transformations in order to act is termed a prodrug. Acetylation is an important modification of proteins in cell biology; and proteomics studies have identified thousands of acetylated mammalian proteins. Acetylation occurs as a co-translational and post-translational modification of proteins, for example, histones, p53, and tubulins. Among these proteins, chromatin proteins and metabolic enzymes are highly represented, indicating that acetylation has a considerable impact on gene expression and metabolism. In bacteria, 90% of proteins involved in central metabolism of Salmonella enterica are acetylated.

N-terminal acetylation

N-terminal acetylation is one of the most common co-translational covalent modifications of proteins in eukaryotes, and it is crucial for the regulation and function of different proteins. N-terminal acetylation plays an important role in the synthesis, stability and localization of proteins. About 85% of all human proteins and 68% in yeast are acetylated at their Nα-terminus. Several proteins from prokaryotes and archaea are also modified by N-terminal acetylation. N-terminal Acetylation is catalyzed by a set of enzyme complexes, the N-terminal acetyltransferases (NATs). NATs transfer an acetyl group from acetyl-coenzyme A (Ac-CoA) to the α-amino group of the first amino acid residue of the protein. Different NATs are responsible for the acetylation of nascent protein N-terminal, and the acetylation was found to be irreversible so far.

N-terminal acetyltransferases To date, seven different NATs have been found in humans - NatA, NatB, NatC, NatD, NatE, NatF and NatH. Each of these different enzyme complexes is specific for different amino acids or amino acid sequences which is shown in the following table. Table 1. The Composition and Substrate specificity of NATs.

NatA

NatA is composed of two subunits, the catalytic subunit Naa10 and the auxiliary subunit Naa15. NatA subunits are more complex in higher eukaryotes than in lower eukaryotes. In addition to the genes NAA10 and NAA15, the mammal-specific genes NAA11 and NAA16, make functional gene products, which form different active NatA complexes. Four possible hNatA catalytic-auxiliary dimers are formed by these four proteins. However, Naa10/Naa15 is the most abundant NatA. NatA acetylates Ser, Ala-, Gly-, Thr-, Val- and Cys N-termini after the initiator methionine is removed by methionine amino-peptidases. These amino acids are more frequently expressed in the N-terminal of proteins in eukaryotes, so NatA is the major NAT corresponding to the whole number of its potential substrates. Several different interaction partners are involved in the N-terminal acetylation by NatA. Huntingtin interacting protein K (HYPK) interacts with hNatA on the ribosome to affect the N-terminal acetylation of a subset of NatA substrates. Subunits hNaa10 and hNaa15 will increase the tendency for aggregation of Huntingtin if HYPK is depleted. Hypoxia-inducible factor (HIF)-1α has also been found to interact with hNaa10 to inhibit hNaa10-mediated activation of β-catenin transcriptional activity.

NatB NatB complexes are composed of the catalytic subunit Naa20p and the auxiliary subunit Naa25p, which are both found in yeast and humans. In yeast, all the NatB subunits are ribosome-associated; but in humans, NatB subunits are both found to be ribosome-associated and non-ribosomal form. NatB acetylates the N-terminal methionine of substrates starting with Met-Glu-, Met-Asp-, Met-Asn- or Met-Gln- N termini.

NatC NatC complex consists of one catalytic subunit Naa30p and two auxiliary subunits Naa35p and Naa38p. All three subunits are found on the ribosome in yeast, but they are also found in non-ribosomal NAT forms like Nat2. NatC complex acetylates the N-terminal methionine of substrates Met-Leu-, Met-Ile-, Met-Trp- or Met-Phe N-termini.

NatD NatD is only composed with the catalytic unit Naa40p and Naa40p and it is conceptually different form the other NATs. At first, only two substrates, H2A and H4 have been identified in yeast and humans. Secondly, the substrate specificity of Naa40p lies within the first 30-50 residues which are quite larger than the substrate specificity of other NATs. The acetylation of histones by NatD is partially associate with ribosomes and the amino acids substrates are the very N-terminal residues, which makes it different from lysine N-acetyltransferases (KATs).

NatE NatE complex consists with subunit Naa50p and two NatA subunits, Naa10p and Naa15p. The N terminus of Naa50p substrates is different from those acetylated by the NatA activity of Naa10p. NAA50 in plants is essential to control plant growth, development, and stress responses and NAA50 function is highly conserved between humans and plants.

NatF

NatF is a NAT that is composed of the Naa60 enzyme. Initially, it was thought that NatF was only found in higher eukaryotes, since it was absent from yeast. However, it was later found that Naa60 is found throughout the eukaryotic domain, but was secondarily lost in the fungi lineage. Compared to yeast, NatF contributes to the higher abundance of N-terminal acetylation in humans. NatF complex acetylates the N-terminal methionine of substrates Met-Lys-, Met-Leu-, Met-Ile-, Met-Trp- and Met-Phe N termini which are partly overlapping with NatC and NatE. NatF has been shown to have an organellar localization and acetylates cytosolic N-termini of transmembrane proteins. The organellar localization of Naa60 is mediated by its unique C-terminus, which consists of two alpha helices that peripherally associate with the membrane and mediate interactions with PI(4)P.

NAA80/NatH NAA80/NatH is an N-terminal acetyltransferase that specifically acetylates the N-terminus of actin.

N-terminal acetylation function

… excerpt ends here. Continue reading the full article.

Illustrations

Worked examples

Example 1 — a first encounter with Protein acetylation

Start with the simplest possible case. Write down what Protein acetylation claims or describes in one sentence, then invent the smallest concrete situation in which that sentence is true. In biology, the smallest case is usually a single object, a single equation or a single measurement. Check that every symbol or term in your sentence has a meaning in that case.

Example 2 — changing one variable

Take the situation from Example 1 and change exactly one quantity: double it, halve it, or set it to zero. Predict what should happen to Protein acetylation before you calculate. Comparing your prediction with the result is the fastest way to find out whether you understand the idea or only the words.

Example 3 — an exam-style question

Typical questions about Protein acetylation ask you to (a) state it precisely, (b) apply it to given data, and (c) explain a limitation. Practise writing all three answers in under five minutes; the third part is what separates a full-mark answer from an average one.

Applications of Protein acetylation

In research: Protein acetylation appears in biology research whenever the underlying quantities have to be modelled precisely. Papers usually cite it as a starting assumption and then explore where it breaks down.
In technology and industry: Engineering practice reuses Protein acetylation in design rules, simulations and safety margins. Knowing the idea lets you read a specification sheet and understand why the numbers look the way they do.
In the classroom: Protein acetylation is common in secondary-school and first-year university syllabi. It links to neighbouring topics Post-translational modification, so understanding it makes those chapters shorter.
In everyday life: Look for Protein acetylation outside the textbook — in sport, cooking, traffic, electronics or the sky above you. An example you found yourself is remembered far longer than one you were given.

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How to study Protein acetylation in 20 minutes

Read the reference excerpt below once, without taking notes.
Close the page and write down what Protein acetylation means in your own words.
Compare your version with the excerpt and mark what you missed.
Work through the three examples above with pen and paper.
Explain Protein acetylation out loud to somebody else — or to Teacher Smith in the lgStudy chat.

Frequently asked questions

What is Protein acetylation in simple terms?

Why does Protein acetylation matter?

Because it connects several biology ideas at once: it gives you a definition you can apply, a quantity you can calculate, and a way to check whether a result is plausible.

How should I study Protein acetylation?

Read the excerpt, restate it from memory, then work through the examples and applications listed on this page. The five-step study plan above takes about twenty minutes.

What does this page cover?

It gives you a compact reference excerpt plus original lgStudy explanations, examples, applications and study material on Protein acetylation.