KDEL is a
target peptide
Target may refer to:
Physical items
* Shooting target, used in marksmanship training and various shooting sports
** Bullseye (target), the goal one for which one aims in many of these sports
** Aiming point, in field artillery, fi ...
sequence in mammals and plants
located on the C-terminal end of the
amino acid
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...
structure of a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
. The KDEL sequence prevents a protein from being secreted from the
endoplasmic reticulum
The endoplasmic reticulum (ER) is, in essence, the transportation system of the eukaryotic cell, and has many other important functions such as protein folding. It is a type of organelle made up of two subunits – rough 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
The Golgi apparatus (), also known as the Golgi complex, Golgi body, or simply the Golgi, is an organelle found in most eukaryotic cells. Part of the endomembrane system in the cytoplasm, it packages proteins into membrane-bound vesicles ins ...
by retrograde transport to the ER lumen. It also targets proteins from other locations (such as the
cytoplasm
In cell biology, the cytoplasm is all of the material within a eukaryotic cell, enclosed by the cell membrane, except for the cell nucleus. The material inside the nucleus and contained within the nuclear membrane is termed the nucleoplasm. The ...
) 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:
*K—
Lysine
Lysine (symbol Lys or K) is an α-amino acid that is a precursor to many proteins. It contains an α-amino group (which is in the protonated form under biological conditions), an α-carboxylic acid group (which is in the deprotonated −C ...
*D—
Aspartic acid
Aspartic acid (symbol Asp or D; the ionic form is known as aspartate), is an α-amino acid that is used in the biosynthesis of proteins. Like all other amino acids, it contains an amino group and a carboxylic acid. Its α-amino group is in the pro ...
*E—
Glutamic acid
Glutamic acid (symbol Glu or E; the ionic form is known as glutamate) is an α-amino acid that is used by almost all living beings in the biosynthesis of proteins. It is a non-essential nutrient for humans, meaning that the human body can synt ...
*L—
Leucine
Leucine (symbol Leu or L) is an essential amino acid that is used in the biosynthesis of proteins. Leucine is an α-amino acid, meaning it contains an α-amino group (which is in the protonated −NH3+ form under biological conditions), an α- ca ...
Therefore, the KDEL sequence in three letter code is:
Lys-
Asp
Asp may refer to:
Places
* Asp, part of Densbüren, Aargau, Switzerland
* Aspe (''Asp'' in Valencian), Alicante, Spain
* Asp Lake, a lake in Minnesota
Animals
* Asp (fish)
* Asp (snake), in antiquity, one of several venomous snakes
** ''Cera ...
-
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
The Coat Protein Complex II, or COPII, is a group of proteins that facilitate the formation of vesicles to transport proteins from the endoplasmic reticulum to the Golgi apparatus or endoplasmic-reticulum–Golgi intermediate compartment. This ...
coated vesicles. The transportation mechanism of proteins containing the KDEL signal sequence is facilitated by KDEL receptors attached to
COPII
The Coat Protein Complex II, or COPII, is a group of proteins that facilitate the formation of vesicles to transport proteins from the endoplasmic reticulum to the Golgi apparatus or endoplasmic-reticulum–Golgi intermediate compartment. This ...
and
COPI
COPI is a coatomer, a protein complex that coats vesicles transporting proteins from the ''cis'' end of the Golgi complex
The Golgi apparatus (), also known as the Golgi complex, Golgi body, or simply the Golgi, is an organelle found in most ...
vesicles.
KDEL receptors
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. 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)
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)
of the ER, resulting in the release of the target protein/ligand.
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.
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.
Equivalent in yeasts and plants
The similar sequence
HDEL performs the same function in
yeast
Yeasts are eukaryotic, single-celled microorganisms classified as members of the fungus kingdom. The first yeast originated hundreds of millions of years ago, and at least 1,500 species are currently recognized. They are estimated to constitut ...
s,
while
plant
Plants are predominantly photosynthetic eukaryotes of the kingdom Plantae. Historically, the plant kingdom encompassed all living things that were not animals, and included algae and fungi; however, all current definitions of Plantae exclud ...
s are known to utilize both KDEL and HDEL signaling sequences.
The abbreviation HDEL follows the same notation as KDEL:
*H—
Histidine
Histidine (symbol His or H) is an essential amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated –NH3+ form under biological conditions), a carboxylic acid group (which is in the de ...
*D—
Aspartic acid
Aspartic acid (symbol Asp or D; the ionic form is known as aspartate), is an α-amino acid that is used in the biosynthesis of proteins. Like all other amino acids, it contains an amino group and a carboxylic acid. Its α-amino group is in the pro ...
*E—
Glutamic acid
Glutamic acid (symbol Glu or E; the ionic form is known as glutamate) is an α-amino acid that is used by almost all living beings in the biosynthesis of proteins. It is a non-essential nutrient for humans, meaning that the human body can synt ...
*L—
Leucine
Leucine (symbol Leu or L) is an essential amino acid that is used in the biosynthesis of proteins. Leucine is an α-amino acid, meaning it contains an α-amino group (which is in the protonated −NH3+ form under biological conditions), an α- ca ...
Three letter code is:
His
His or HIS may refer to:
Computing
* Hightech Information System, a Hong Kong graphics card company
* Honeywell Information Systems
* Hybrid intelligent system
* Microsoft Host Integration Server
Education
* Hangzhou International School, in ...
-
Asp
Asp may refer to:
Places
* Asp, part of Densbüren, Aargau, Switzerland
* Aspe (''Asp'' in Valencian), Alicante, Spain
* Asp Lake, a lake in Minnesota
Animals
* Asp (fish)
* Asp (snake), in antiquity, one of several venomous snakes
** ''Cera ...
-
Glu-
Leu.
See also
*
ER retention ER retention refers to proteins that are retained in the endoplasmic reticulum, or ER, after folding; these are known as ER resident proteins.
Protein localization to the ER often depends on certain sequences of amino acids located at the N terminu ...
*
KKXX (amino acid sequence) KKXX and for some proteins XKXX is a target peptide motif located in the C terminus in the amino acid structure of a protein responsible for retrieval of endoplasmic reticulum (ER) membrane proteins to and from the Golgi apparatus. These ER membran ...
* Endoplasmic reticulum protein retention receptors
**
KDELR1
KDEL (Lys-Asp-Glu-Leu) endoplasmic reticulum protein retention receptor 1, also known as KDELR1, is a protein which in humans is encoded by the ''KDELR1'' gene.
Function
Retention of resident soluble proteins in the lumen of the endoplasmic r ...
**
KDELR2
ER lumen protein retaining receptor 2 is a protein that in humans is encoded by the ''KDELR2'' gene.
Retention of resident soluble proteins in the lumen of the endoplasmic reticulum (ER) is achieved in both yeast and animal cells by their continua ...
**
KDELR3
ER lumen protein retaining receptor 3 is a protein that in humans is encoded by the ''KDELR3'' gene.
Retention of resident soluble proteins in the lumen of the endoplasmic reticulum (ER) is achieved in both yeast and animal cells by their continua ...
References
{{reflist
Amino acids
Amino acid motifs
Peptide sequences