close
This essay has been submitted by a student. This is not an example of the work written by professional essay writers.

A Proteasomal Degradation Process of Ubiquitination

  • Subject: Science
  • Category: Genetics
  • Essay Topic: DNA, Gene
  • Pages: 2
  • Words: 747
  • Published: 15 January 2019
  • Downloads: 27
downloadDownload printPrint

Remember! This is just a sample.

You can get your custom paper by one of our expert writers.

Get custom essay

121 writers online

blank-ico
Download PDF

Ubiquitination, a proteasomal degradation process, is based on covalent attachment of ubiquitin to a substrate lysine on a target protein, marking the protein for its degradation. This process renews intracellular proteins balancing the rate of degradation with the rate of protein synthesis, resulting in homeostasis. Homeostasis is achieved by eliminating damaged proteins which typically result in disease as they compete with functional proteins for binding sites/partners.

In addition to homeostasis, the process also regulates cell cycle progression, gene transcription, DNA repair, apoptosis and receptor endocytosis, some of which require lysosomal degradation. However, the UPS (ubiquitin proteasome system) differs from the UBL (ubiquitin like system) and from the lysosomal pathway (requiring autophagy for degradation). The 76AA ubiquitin molecule contains 7 lysine residues allowing the formation of isopeptide linked chains or Met1 chains (ubiquitin linked ubiquitin). The predominant linkage being Lys 48 due to its degradation role usually allows polyubiquitination to occur, with the Lys 63 linkage known for its non-degradation role and subsequent activation of pathways such as PKB/AKT. Following the covalent addition of the ubiquitin chain, the regulatory mechanism involves three enzymes in a cascade of activation, conjugation and ligation resulting in the degradation of the target protein by the 26s proteasome.

Initiation of the mechanism occurs through activation of ubiquitin in an ATP dependent manner by E1. A thioester bond results upon activation between the ubiquitin C terminus and an active cysteine on E1. E2, the ubiquitin-conjugating enzyme, then binds with E1, transferring the ubiquitin to E2 at a catalytic cysteine residue. The final enzyme involved in the process, E3, ubiquitin ligase, forms a complex with E2 through an isopeptide bond, facilitating the transfer of ubiquitin to the substrate protein. Formation of this isopeptide bond occurs at the amino group of lysine in the substrate and the C terminal glycine residue of the ubiquitin molecule (Fig.1). Considering E3 is the final enzyme involved in the cascade, it determines specificity of the substrate. With a large number of substrates available, a large ligase family must also exist (>700 members). The E1 family, which typically lack specificity for E2 or E3 only contain 2 members in humans, however the E2 family comprises of 40 members as its main role determines which polyubiquitin chains are catalysed by E3.

Classification of the E3 ligase family is crucial, impacting the mechanism in which conjugation to the substrate occurs. Classification varies but was observed by Francesca Morreale, University of Dundee, Scotland as a 3 member family including: RING (Really Interesting New Gene) and U-box (UFD2 homology), RBR (Ring in-Between Ring) and HECT (homologous to E6-associated protein C-terminus), each with a varying mechanism of action. The most prevalent being, RING, which act as mediators, directly transferring ubiquitin from E2 to the substrate, never binding with ubiquitin itself but acting as a scaffold ensuring a flexible E2 orientation for the substrate. These ligases are comprised of a zinc binding domain and possess the ability to act as monomers, homodimers or heterodimers. Homodimer RING ligases allow the binding of an E2 per monomer, resulting in two E2’s bound. Similarly, U-box ligases contain a RING structure however lacking the zinc domain and potentially act as monomers and homodimers however, their main role involves completing polyubiquitin elongation, previously begun by another ligase. RING ligases are often classified based on their multiple subunit composition such as cullin ring ligases (CRL) comprised of a cullin scaffold or anaphase-promoting complex/cyclosome (APC/C) composed of 19 subunits, including a ring subunit (Apc11) and a cullin-like subunit (Apc2).

HECT ligases function by a varying mechanism comprised of two steps. Ubiquitin forms an intermediate bond with the catalytic cysteine on E3 prior to its transfer to the target protein. This domain, positioned at the C terminus of proteins contains an N-terminal lobe and C-terminal lobe structure, allowing specificity of the substrate and catalysis respectively. Subfamilies such as Nedd4 and HERC exist here due to varying N termini. The final group of ligases, RBR posses the same mechanism of action as the HECT ligase family however, differ in structure. RBR ligases are comprised of two RING structures, one which recruits the E2 molecule (ubiquitin charged) and the second containing the catalytic cysteine. Proteasomal degradation is an irreversible process once the target protein reaches the proteasome. It is comprised of at least one 20s regulatory particle (RP), for substrate recognition and a 19S hollow core particle (CP) typically comprised of alpha and beta subunits, completing the degradation of the unfolded protein. However, prior to this step, ubiquitination is potentially reversible.

Remember: This is just a sample from a fellow student.

Your time is important. Let us write you an essay from scratch

experts 450+ experts on 30 subjects ready to help you just now

delivery Starting from 3 hours delivery

Find Free Essays

We provide you with original essay samples, perfect formatting and styling

Cite this Essay

To export a reference to this article please select a referencing style below:

A Proteasomal Degradation Process of Ubiquitination. (2019, January 15). GradesFixer. Retrieved August 6, 2022, from https://gradesfixer.com/free-essay-examples/a-proteasomal-degradation-process-of-ubiquitination/
“A Proteasomal Degradation Process of Ubiquitination.” GradesFixer, 15 Jan. 2019, gradesfixer.com/free-essay-examples/a-proteasomal-degradation-process-of-ubiquitination/
A Proteasomal Degradation Process of Ubiquitination. [online]. Available at: <https://gradesfixer.com/free-essay-examples/a-proteasomal-degradation-process-of-ubiquitination/> [Accessed 6 Aug. 2022].
A Proteasomal Degradation Process of Ubiquitination [Internet]. GradesFixer. 2019 Jan 15 [cited 2022 Aug 6]. Available from: https://gradesfixer.com/free-essay-examples/a-proteasomal-degradation-process-of-ubiquitination/
copy to clipboard
close

Where do you want us to send this sample?

    By clicking “Continue”, you agree to our terms of service and privacy policy.

    close

    Be careful. This essay is not unique

    This essay was donated by a student and is likely to have been used and submitted before

    Download this Sample

    Free samples may contain mistakes and not unique parts

    close

    Sorry, we could not paraphrase this essay. Our professional writers can rewrite it and get you a unique paper.

    close

    Thanks!

    Please check your inbox.

    We can write you a custom essay that will follow your exact instructions and meet the deadlines. Let's fix your grades together!

    boy

    Hi there!

    Are you interested in getting a customized paper?

    Check it out!
    Don't use plagiarized sources. Get your custom essay. Get custom paper
    exit-popup-close

    Haven't found the right essay?

    Get an expert to write you the one you need!

    exit-popup-print

    Professional writers and researchers

    exit-popup-quotes

    Sources and citation are provided

    exit-popup-clock

    3 hour delivery

    exit-popup-persone