Oligosaccharyltransferase
Encyclopedia
Oligosaccharyltransferase or OST is a membrane protein
complex
that transfers a 14-sugar
oligosaccharide
from dolichol
to nascent protein
. It is a type of glycosyltransferase
. The sugar Glc3Man9GlcNAc2 (where Glc=Glucose
, Man=Mannose
, and GlcNAc=N-acetylglucosamine
) is attached to an asparagine
(Asn) residue in the sequence Asn-X-Ser
or Asn-X-Thr
where X is any amino acid except proline
. This sequence is called a glycosylation sequon
. The reaction catalyzed by OST is the central step in the N-linked glycosylation pathway
.
in the endoplasmic reticulum
(ER) membrane. The active site of OST is located about 4 nm from the lumenal face of the ER membrane . It usually acts during translation as the nascent protein is entering the ER, but this cotranslational glycosylation is nevertheless called a posttranslational modification
. A few examples have been found of OST activity after translation is complete , . Current opinion is that post-translational activity may occur if the protein is poorly folded
or folds slowly .
s, and three of the eight proteins are glycosylated themselves, . OST in mammals is known to have a similar composition.
OST is thought to require many subunits because it must:
Congenital disorder
CDG syndrome
s are genetic disorder
s of the glycosylation pathway. They are labelled "Type I" if the defective gene
is for an enzyme
involved in the assembly or transfer of the Glc3Man9GlcNAc2-dolichol precursor. They are labelled "Type II" if the defective step occurs after the action of OST in the N-linked glyocsylation pathway or involves O-linked glycosylation.
Membrane protein
A membrane protein is a protein molecule that is attached to, or associated with the membrane of a cell or an organelle. More than half of all proteins interact with membranes.-Function:...
complex
Protein complex
A multiprotein complex is a group of two or more associated polypeptide chains. If the different polypeptide chains contain different protein domain, the resulting multiprotein complex can have multiple catalytic functions...
that transfers a 14-sugar
Sugar
Sugar is a class of edible crystalline carbohydrates, mainly sucrose, lactose, and fructose, characterized by a sweet flavor.Sucrose in its refined form primarily comes from sugar cane and sugar beet...
oligosaccharide
Oligosaccharide
An oligosaccharide is a saccharide polymer containing a small number of component sugars, also known as simple sugars...
from dolichol
Dolichol
Dolichol refers to any of a group of long-chain mostly unsaturated organic compounds that are made up of varying numbers of isoprene units terminating in an α-saturated isoprenoid group, containing an alcohol functional group.-Functions:...
to nascent protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
. It is a type of glycosyltransferase
Glycosyltransferase
Glycosyltransferases are enzymes that act as a catalyst for the transfer of a monosaccharide unit from an activated nucleotide sugar to a glycosyl acceptor molecule, usually an alcohol....
. The sugar Glc3Man9GlcNAc2 (where Glc=Glucose
Glucose
Glucose is a simple sugar and an important carbohydrate in biology. Cells use it as the primary source of energy and a metabolic intermediate...
, Man=Mannose
Mannose
Mannose is a sugar monomer of the aldohexose series of carbohydrates. Mannose is a C-2 epimer of glucose. It is not part of human metabolism, but is a component of microbial cell walls, and is therefore a target of the immune system and also of antibiotics....
, and GlcNAc=N-acetylglucosamine
N-Acetylglucosamine
N-Acetylglucosamine is a monosaccharide derivative of glucose. It is an amide between glucosamine and acetic acid...
) is attached to an asparagine
Asparagine
Asparagine is one of the 20 most common natural amino acids on Earth. It has carboxamide as the side-chain's functional group. It is not an essential amino acid...
(Asn) residue in the sequence Asn-X-Ser
Serine
Serine is an amino acid with the formula HO2CCHCH2OH. It is one of the proteinogenic amino acids. By virtue of the hydroxyl group, serine is classified as a polar amino acid.-Occurrence and biosynthesis:...
or Asn-X-Thr
Threonine
Threonine is an α-amino acid with the chemical formula HO2CCHCHCH3. Its codons are ACU, ACA, ACC, and ACG. This essential amino acid is classified as polar...
where X is any amino acid except proline
Proline
Proline is an α-amino acid, one of the twenty DNA-encoded amino acids. Its codons are CCU, CCC, CCA, and CCG. It is not an essential amino acid, which means that the human body can synthesize it. It is unique among the 20 protein-forming amino acids in that the α-amino group is secondary...
. This sequence is called a glycosylation sequon
Sequon
A sequon is a sequence of three consecutive amino acids in a proteinthat can serve as the attachment site to a polysaccharide called anN-linked-Glycan. This is a polysaccharidelinked to the protein via the nitrogen atom in the side chain of...
. The reaction catalyzed by OST is the central step in the N-linked glycosylation pathway
Metabolic pathway
In biochemistry, metabolic pathways are series of chemical reactions occurring within a cell. In each pathway, a principal chemical is modified by a series of chemical reactions. Enzymes catalyze these reactions, and often require dietary minerals, vitamins, and other cofactors in order to function...
.
Location
OST is a component of the transloconTranslocon
The translocon is the complex of proteins associated with the translocation of nascent polypeptides across membranes. In eukaryotes the polypeptides are transported into the interior space of the endoplasmic reticulum from the cytosol...
in the endoplasmic reticulum
Endoplasmic reticulum
The endoplasmic reticulum is an organelle of cells in eukaryotic organisms that forms an interconnected network of tubules, vesicles, and cisternae...
(ER) membrane. The active site of OST is located about 4 nm from the lumenal face of the ER membrane . It usually acts during translation as the nascent protein is entering the ER, but this cotranslational glycosylation is nevertheless called a posttranslational modification
Posttranslational modification
Posttranslational modification is the chemical modification of a protein after its translation. It is one of the later steps in protein biosynthesis, and thus gene expression, for many proteins....
. A few examples have been found of OST activity after translation is complete , . Current opinion is that post-translational activity may occur if the protein is poorly folded
Protein folding
Protein folding is the process by which a protein structure assumes its functional shape or conformation. It is the physical process by which a polypeptide folds into its characteristic and functional three-dimensional structure from random coil....
or folds slowly .
Structure and function
Yeast OST is composed of eight different membrane-spanning proteins in three subcomplexes, . These octomers do not form higher order oligomerOligomer
In chemistry, an oligomer is a molecule that consists of a few monomer units , in contrast to a polymer that, at least in principle, consists of an unlimited number of monomers. Dimers, trimers, and tetramers are oligomers. Many oils are oligomeric, such as liquid paraffin...
s, and three of the eight proteins are glycosylated themselves, . OST in mammals is known to have a similar composition.
OST is thought to require many subunits because it must:
- 1) Position itself near the translocon pore.
- 2) Recognize and bind oligosaccharyldolichol.
- 3) Scan the nascent protein in order to recognize and bind sequons.
- 4) Move these two large substrates into their proper locations and conformations.
- 5) Activate the AsnAsparagineAsparagine is one of the 20 most common natural amino acids on Earth. It has carboxamide as the side-chain's functional group. It is not an essential amino acid...
amideAmideIn chemistry, an amide is an organic compound that contains the functional group consisting of a carbonyl group linked to a nitrogen atom . The term refers both to a class of compounds and a functional group within those compounds. The term amide also refers to deprotonated form of ammonia or an...
nitrogenNitrogenNitrogen is a chemical element that has the symbol N, atomic number of 7 and atomic mass 14.00674 u. Elemental nitrogen is a colorless, odorless, tasteless, and mostly inert diatomic gas at standard conditions, constituting 78.08% by volume of Earth's atmosphere...
atom for the actual transfer of oligosaccharide. - 6) Release its substrates.
Congenital disorderCongenital disorderA congenital disorder, or congenital disease, is a condition existing at birth and often before birth, or that develops during the first month of life , regardless of causation...
s of glycosylation (CDG) types
CDG syndromeCDG syndrome
A congenital disorder of glycosylation is one of several rare inborn errors of metabolism in which glycosylation of a variety of tissue proteins and/or lipids is deficient or defective. Congenital disorders of glycosylation are sometimes known as CDG syndromes...
s are genetic disorder
Genetic disorder
A genetic disorder is an illness caused by abnormalities in genes or chromosomes, especially a condition that is present from before birth. Most genetic disorders are quite rare and affect one person in every several thousands or millions....
s of the glycosylation pathway. They are labelled "Type I" if the defective gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
is for an enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
involved in the assembly or transfer of the Glc3Man9GlcNAc2-dolichol precursor. They are labelled "Type II" if the defective step occurs after the action of OST in the N-linked glyocsylation pathway or involves O-linked glycosylation.