Oligosaccharyltransferase or OST () is a

membrane protein Membrane proteins are common proteins that are part of, or interact with, biological membranes. Membrane proteins fall into several broad categories depending on their location. Integral membrane proteins are a permanent part of a cell membrane ...

complex Complex commonly refers to: * Complexity, the behaviour of a system whose components interact in multiple ways so possible interactions are difficult to describe ** Complex system, a system composed of many components which may interact with each ...

that transfers a 14-

sugar Sugar is the generic name for sweet-tasting, soluble carbohydrates, many of which are used in food. Simple sugars, also called monosaccharides, include glucose Glucose is a sugar with the Chemical formula#Molecular formula, molecul ...

oligosaccharide An oligosaccharide (; ) is a carbohydrate, saccharide polymer containing a small number (typically three to ten) of monosaccharides (simple sugars). Oligosaccharides can have many functions including Cell–cell recognition, cell recognition and ce ...

from

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 Dolicho ...

to nascent

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

. It is a type of

glycosyltransferase Glycosyltransferases (GTFs, Gtfs) are enzymes ( EC 2.4) that establish natural glycosidic linkages. They catalyze the transfer of saccharide moieties from an activated nucleotide sugar (also known as the "glycosyl donor") to a nucleophilic gl ...

. The sugar Glc₃Man₉GlcNAc₂ (where Glc=

Glucose Glucose is a sugar with the Chemical formula#Molecular formula, molecular formula , which is often abbreviated as Glc. It is overall the most abundant monosaccharide, a subcategory of carbohydrates. It is mainly made by plants and most algae d ...

, Man=

Mannose Mannose is a sugar with the formula , which sometimes is abbreviated Man. It is one of the monomers of the aldohexose series of carbohydrates. It is a C-2 epimer of glucose. Mannose is important in human metabolism, especially in the glycosylatio ...

, and GlcNAc= ''N''-acetylglucosamine) is attached to an

asparagine Asparagine (symbol Asn or N) is an α-amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated −NH form under biological conditions), an α-carboxylic acid group (which is in the depro ...

(Asn) residue in the sequence Asn-X- Ser or Asn-X- Thr where X is any amino acid except

proline Proline (symbol Pro or P) is an organic acid classed as a proteinogenic amino acid (used in the biosynthesis of proteins), although it does not contain the amino group but is rather a secondary amine. The secondary amine nitrogen is in the p ...

. This sequence is called a glycosylation ''

sequon A sequon is a sequence of consecutive amino acids in a protein that can serve as the attachment site to a polysaccharide, frequently an N-linked-Glycan. The polysaccharide is linked to the protein via the nitrogen atom in the side chain of asparagi ...

.'' The reaction catalyzed by OST is the central step in the ''N''-linked glycosylation pathway.

Location

OST is a component of the

translocon The translocon (also known as a translocator or translocation channel) is a complex of proteins associated with the translocation of polypeptides across membranes. In eukaryotes the term translocon most commonly refers to the complex that transpor ...

in the

endoplasmic reticulum The endoplasmic reticulum (ER) is a part of a transportation system of the eukaryote, eukaryotic cell, and has many other important functions such as protein folding. The word endoplasmic means "within the cytoplasm", and reticulum is Latin for ...

(ER)

membrane A membrane is a selective barrier; it allows some things to pass through but stops others. Such things may be molecules, ions, or other small particles. Membranes can be generally classified into synthetic membranes and biological membranes. Bi ...

. A lipid-linked core-oligosaccharide is assembled at the membrane of the endoplasmic reticulum and transferred to selected

residues of nascent

polypeptide Peptides are short chains of amino acids linked by peptide bonds. A polypeptide is a longer, continuous, unbranched peptide chain. Polypeptides that have a molecular mass of 10,000 Da or more are called proteins. Chains of fewer than twenty ...

chains by the oligosaccharyl transferase

. The active site of OST is located about 4 nm from the lumenal face of the ER membrane. It usually acts during

translation Translation is the communication of the semantics, meaning of a #Source and target languages, source-language text by means of an Dynamic and formal equivalence, equivalent #Source and target languages, target-language text. The English la ...

as the nascent protein is entering the ER, but this cotranslational glycosylation is nevertheless called a

posttranslational modification In molecular biology, post-translational modification (PTM) is the covalent process of changing proteins following protein biosynthesis. PTMs may involve enzymes or occur spontaneously. Proteins are created by ribosomes, which translate mRNA ...

. 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.

Structure and function

Yeast OST is composed of eight different membrane-spanning proteins in three subcomplexes (one of them is

OST4 In molecular biology, OST4 (Dolichyl-diphosphooligosaccharide—protein glycosyltransferase subunit 4) is a subunit of the oligosaccharyltransferase complex. OST4 is a very short, approximately 30 amino acids, protein found from fungi to vertebra ...

). These octomers do not form higher order

oligomer In chemistry and biochemistry, an oligomer () is a molecule that consists of a few repeating units which could be derived, actually or conceptually, from smaller molecules, monomers.Quote: ''Oligomer molecule: A molecule of intermediate relativ ...

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: #Position itself near the translocon pore. #Recognize and bind oligosaccharyldolichol. #Scan the nascent protein in order to recognize and bind sequons. #Move these two large substrates into their proper locations and conformations. #Activate the Asn

amide In organic chemistry, an amide, also known as an organic amide or a carboxamide, is a chemical compound, compound with the general formula , where R, R', and R″ represent any group, typically organyl functional group, groups or hydrogen at ...

nitrogen Nitrogen is a chemical element; it has Symbol (chemistry), symbol N and atomic number 7. Nitrogen is a Nonmetal (chemistry), nonmetal and the lightest member of pnictogen, group 15 of the periodic table, often called the Pnictogen, pnictogens. ...

atom for the actual transfer of oligosaccharide. #Release its substrates. The catalytically active subunit of the OST is called STT3. Two paralogs exist in eukaryotes, termed STT3A and STT3B. STT3A is primarily responsible for cotranslational glycosylation of the nascent polypeptide as it enters the lumen of the endoplasmic reticulum whereas STT3B can also mediate posttranslational glycosylation. The structure of PglB, the prokaryotic homolog of STT3 has been solved. The high sequence similarity between the prokaryotic and the eukaryotic STT3 suggests that their structures are similar.

Clinical significance

CDG syndromes are

genetic disorder A genetic disorder is a health problem caused by one or more abnormalities in the genome. It can be caused by a mutation in a single gene (monogenic) or multiple genes (polygenic) or by a chromosome abnormality. Although polygenic disorders ...

s of the glycosylation pathway. They are labelled "Type I" if the defective

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

is for an

enzyme An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...

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 glycosylation pathway or involves ''O''-linked glycosylation.

References

External links

* {{Glycoprotein metabolism enzymes EC 2.4.1

Location

Structure and function

Clinical significance

See also

References

External links