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KDEL (amino acid sequence)

From Wikipedia, the free encyclopedia

KDEL is a target peptide sequence in mammals and plants[1][2] located on the C-terminal end of the amino acid structure of a protein. The KDEL sequence prevents a protein from being secreted from the endoplasmic reticulum (ER) and facilitates its return if it is accidentally exported.

A protein with a functional KDEL motif will be retrieved from the Golgi apparatus by retrograde transport to the ER lumen.[3] It also targets proteins from other locations (such as the cytoplasm) to the ER. Proteins can only leave the ER after this sequence has been cleaved off.

The abbreviation KDEL is formed by the corresponding letters to each amino acid. This letter system was defined by the IUPAC and IUBMB in 1983, and is as follows:

Therefore, the KDEL sequence in three letter code is: Lys-Asp-Glu-Leu.

The soluble resident protein will remain in the ER as long as it contains a KDEL signal sequence on the C-terminal end of the protein. However, since vesicle budding is such a dynamic process, and there is a high concentration of soluble proteins in the ER, soluble proteins are inadvertently transported to the cis-golgi via COPII coated vesicles. The transportation mechanism of proteins containing the KDEL signal sequence is facilitated by KDEL receptors attached to COPII and COPI vesicles.

KDEL receptors

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Above is a video of HeLa cells that were treated with 160μg/ml of eGFP-RTA. Video starts 30-minutes after toxin treatment, 45 frames/hour.   [4]

KDEL receptors initiate the mechanism by which proteins are transported from the Golgi to the ER. These proteins were originally from the ER and they escaped into the cis-Golgi.[5] The KDEL signal sequence is recognized by KDEL receptors, which are commonly located in the cis-Golgi, lysosomes, and secretory vesicles. These receptors are recycled during each transport cycle. KDEL receptor binding is dependent on pH, in which the ligand (target protein) binds strongly to the receptor in the cis-Golgi due to the unique low pH (6, in in vitro experiments pH 5 shows strongest binding)[6][7] characteristic of the biochemical environment of the cis-Golgi network. As the vesicle that contains the KDEL receptor reaches the ER, the receptor is inactive due to the high pH (7.2-7.4)[8][9][10] of the ER, resulting in the release of the target protein/ligand.[11]

A study conducted by Becker et al. demonstrated through experimentation and simulation that KDEL receptors/cargo clustering at the cell surface is caused by the transport of cargo-synchronized receptors from and to the plasma membrane.[4] The video on the right demonstrates an experiment conducted by Becker et al. demonstrating the dynamics of the KDEL receptor clustering's time dependence with a full experiment from start to finish (60 minutes). Within the paper, the authors note the importance of understanding the mechanism of action of the receptor clustering and dynamic reorganization because of its potential understanding to use for designing targeted therapeutics.[4]

Equivalent in yeasts and plants

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The similar sequence HDEL performs the same function in yeasts,[12] while plants are known to utilize both KDEL and HDEL signaling sequences.[2][1]

The abbreviation HDEL follows the same notation as KDEL:

Three letter code is: His-Asp-Glu-Leu.

See also

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References

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  1. ^ a b Denecke J.; De Rycke R.; Botterman J. (Jun 1992). "Plant and mammalian sorting signals for protein retention in the endoplasmic reticulum contain a conserved epitope". EMBO Journal. 11 (6): 2345–2355. doi:10.1002/j.1460-2075.1992.tb05294.x. PMC 556702. PMID 1376250.
  2. ^ a b Napier R.M.; Fowke L.C.; Hawes C.; Lewis M.; Pelham H.R. (Jun 1992). "Immunological evidence that plants use both HDEL and KDEL for targeting proteins to the endoplasmic reticulum". Journal of Cell Science. 102 (2): 261–271. doi:10.1242/jcs.102.2.261. PMID 1383243.
  3. ^ Mariano Stornaiuolo; Lavinia V. Lotti; Nica Borgese; Maria-Rosaria Torrisi; Giovanna Mottola; Gianluca Martire; Stefano Bonatti (March 2003). "KDEL and KKXX Retrieval Signals Appended to the Same Reporter Protein Determine Different Trafficking between Endoplasmic Reticulum, Intermediate Compartment, and Golgi Complex". Molecular Biology of the Cell. 14 (3): 369–377. doi:10.1091/mbc.E02-08-0468. PMC 151567. PMID 12631711.
  4. ^ a b c Becker, Björn; Shaebani, M. Reza; Rammo, Domenik; Bubel, Tobias; Santen, Ludger; Schmitt, Manfred J. (June 29, 2016). "Cargo binding promotes KDEL receptor clustering at the mammalian cell surface". Scientific Reports. 6: 28940. arXiv:1712.06151. Bibcode:2016NatSR...628940B. doi:10.1038/srep28940. ISSN 2045-2322. PMC 4926219. PMID 27353000.
  5. ^ Yamamoto, Katsushi; Hamada, Hiromichi; Shinkai, Hiroshi; Kohno, Yoichi; Koseki, Haruhiko; Aoe, Tomohiko (2003-09-05). "The KDEL Receptor Modulates the Endoplasmic Reticulum Stress Response through Mitogen-activated Protein Kinase Signaling Cascades". Journal of Biological Chemistry. 278 (36): 34525–34532. doi:10.1074/jbc.M304188200. ISSN 0021-9258. PMID 12821650.
  6. ^ Wilson, Duncan; Lewis, Michael; Pelham, Hugh (1993). "pH-dependent binding of KDEL to its receptor in vitro". Journal of Biological Chemistry. 268 (10): 7465–7468. doi:10.1016/S0021-9258(18)53197-5. PMID 8385108.
  7. ^ Bräuer, Philipp; Parker, Joanne L.; Gerondopoulos, Andreas; Zimmermann, Iwan; Seeger, Markus A.; Barr, Francis A.; Newstead, Simon (2019-03-08). "Structural basis for pH-dependent retrieval of ER proteins from the Golgi by the KDEL receptor". Science. 363 (6431): 1103–1107. Bibcode:2019Sci...363.1103B. doi:10.1126/science.aaw2859. ISSN 0036-8075. PMID 30846601.
  8. ^ Bräuer, Philipp; Parker, Joanne L.; Gerondopoulos, Andreas; Zimmermann, Iwan; Seeger, Markus A.; Barr, Francis A.; Newstead, Simon (2019-03-08). "Structural basis for pH-dependent retrieval of ER proteins from the Golgi by the KDEL receptor". Science. 363 (6431): 1103–1107. Bibcode:2019Sci...363.1103B. doi:10.1126/science.aaw2859. ISSN 0036-8075. PMID 30846601.
  9. ^ Wu, Minnie M.; Llopis, Juan; Adams, Stephen; McCaffery, J. Michael; Kulomaa, Markku S.; Machen, Terry E.; Moore, Hsiao-Ping H.; Tsien, Roger Y. (2000-03-01). "Organelle pH studies using targeted avidin and fluorescein–biotin". Chemistry & Biology. 7 (3): 197–209. doi:10.1016/S1074-5521(00)00088-0. ISSN 1074-5521. PMID 10712929.
  10. ^ Wu, Minnie M.; Grabe, Michael; Adams, Stephen; Tsien, Roger Y.; Moore, Hsiao-Ping H.; Machen, Terry E. (2001-08-31). "Mechanisms of pH Regulation in the Regulated Secretory Pathway". Journal of Biological Chemistry. 276 (35): 33027–33035. doi:10.1074/jbc.M103917200. ISSN 0021-9258. PMID 11402049.
  11. ^ Pagny, Sophie; Lerouge, Patrice; Faye, Loic; Gomord, Veronique (February 1999). "Signals and mechanisms for protein retention in the endoplasmic reticulum". Journal of Experimental Botany. 50 (331): 157–158. doi:10.1093/jexbot/50.331.157.
  12. ^ Dean N.; Pelham HR. (Aug 1990). "Recycling of proteins from the Golgi compartment to the ER in yeast". The Journal of Cell Biology. 111 (2): 369–377. doi:10.1083/jcb.111.2.369. PMC 2116185. PMID 2199456.
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