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84 Cards in this Set
- Front
- Back
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Are proteins just proteins normally?
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No; the majority of proteins contain covalently attached molecules.
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What are 5 molecules commonly added to proteins?
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-Ubiquitin
-Phosphate -Carbohydrates -ADP-ribose -Fatty acids/lipids/choleterol |
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Why is ubiquitin added to proteins?
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It targets proteins for degradation in proteosomes.
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What does phosphate addition do to proteins?
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Activates/inactivates many enzymes
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What is the term for addition of carbohydrates to protein?
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Glycosylation.
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WHY modify proteins?
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To increase the functional diversity of the limited gene pool.
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How many genes are in the human genome?
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~35,000
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What are 2 types of hydrophilic protein modifications?
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1. Oligosaccharide addition (glycosylation)
2. ADP-ribosylation |
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What are 2 types of hydrophobic protein modifications?
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-Fatty acid addition
-Prenylation (Cholesterol addition) |
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Give 2 examples of physiologic conditinos associated w/ hydrophilic modification:
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-ABO blood groups
-Influenza virus |
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What are the effects of Hydrophobic protein modification (fatty acid/prenylation)?
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Membrane association - proteins can act as membrane surface molecules.
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What is the definition of an oligosaccharide?
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Polymer containing 2 or more monosaccharides joined by O-glycosidic linkages.
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Why is glycosylation important?
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It is one of the principal co- and post-translational modifications of membrane proteins, secreted proteins, and the majority of proteins made in rough ER.
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What are the 2 types of glycosylation and what is the gist of each?
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N-linked: glycosylation of amide N of asparagine residues
O-linked: glycosylation of hydroxy oxygen of Ser and Thr residues. |
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Why glycosylate proteins?
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-Assist in folding
-To give stability -Assist in cell-cell adhesion |
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What is the main purpose of N-glycosylation of proteins?
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To assist in proper protein folding.
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What is the 1st step in N-linked glycosylation?
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Addition of a precursor molecule to the target protein.
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What does this precursor molecule consist of?
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3 Glucose
9 mannose 2 N-acetylglucosamine |
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What happens after addition of the precursor molecule to the protein??
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The complex is taken up by the carrier molecule DOLICHOL
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What is the purpose of dolichol?
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To transfer the precursor-protein complex to the correct point on the protein's polypeptide chain.
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What happens as the complex is transferred by Dolichol?
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It is translocated into the ER lumen.
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What happens in the ER lumen?
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An oligosaccharide chain is attached to Asparagine.
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What catalyzes the oligosacch. transfer?
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Oligosaccharyl transferase
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Can an oligosacch. be transferred to just any Asn?
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No; must be in the tripeptide sequences Asn-X-Ser or Asn-X-Thr
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What can X be?
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Any amino acid except Pro
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What is the sequence containing Asn called?
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Glycosylation Sequon
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What happens after the glycosylation reaction?
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Removal of the 3 glucose molecules in the precursor component - if the protein folded correctly.
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Once the protein has correctly folded what happens to the glycoprotein?
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Transport to Golgi for further processing like mannose removal.
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Ok that's the end of wikipedia notes
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ok
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Recap: what type of modification is addition of oligosaccharides to protein?
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Hydrophilic
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What is an oligosaccharide?
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A polymer of sugar molecules containing 2 or more monosaccharides joined by O-glycosidic linkages
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Of the carbs generally found in mammals, which is not usually in glycolipids/GAGs?
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Mannose
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Which 2 are epimers?
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GalNac and Glcnac
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What are the 3 predominant sugars in glycosaminoglycans?
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-Xylose
-Glucaronic acid -Iduronic acid |
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What is the significant feature that makes these 3 sugars good for GAGs?
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They are negatively charged.
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What must happen to monosaccharides before they can be added to protein?
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Acitvation - to make NT sugars
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What are nucleotide sugars?
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Activated, hi-energy compounds
-The immediate precursors of glycoprotein/lipid synth. |
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Where does sugar activation occur?
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In the cytoplasm - EXCEPT FOR SIALIC ACID
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Where does activation of sialic acid occur?
What does it produce? |
Nucleus
-Product is CMP-sialic acid |
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What is the actual reaction for NT sugar synthesis
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NTP + Sugar 1-phosphate -> Sugar NDP + PPi
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What is the actual reaction for CMP-sialic acid?
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CTP + sialic acid -> CMP-sialic acid + PPi
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What are 2 methods in which NT sugars can be synthesized?
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-De novo
-Epimerization |
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What is the major in vivo source of monosaccharide components in glycoproteins and glycolipids?
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GLUCOSE
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What is a major requirement of NT sugar synthesis?
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ENERGY - Lots of ATP
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What enzymes catalyze glycosylation?
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Glycosyltransferases
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Where are Glycosyltransferases found?
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In the membranes of the ER and Golgi body
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What exactly do glycosyltransferases do?
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Transfer sugar from an activated donor (NT sugar) to an acceptor target (protein or other).
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What is the important characteristic of glycosyltransferases?
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Their specificity for:
1. Sugar transferred 2. Substrate transferred TO 3. Type of linkage created |
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How many glycosyltransferases are there?
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Over 300
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What do the glycosyltransferases do in N-glycosylation?
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Build up the oligosaccharide chain precursor molecule.
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How many glycosyltransferases operate in this process?
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7 - on the cytosolic face of RER.
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Where does ea. take place:
-N glycosylation -O glycosylation |
N - in the RER lumen, processing in Golgi
O - in the Golgi |
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Where do NT sugars tend to be?
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Cytosol - so they need transporters for uptake into the RER and golgi
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How do glycoproteins get to their destination after synthesis?
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By vesicular transport from the lumen to the cytosol.
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What are the 3 major types of carbohydrate-protein linkages?
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1. N-linkage btwn GlcNAc and Asn
2. O-linkage btwn GalNAc and Ser(Thr) 3. O-linkage betwn Xyl and Ser |
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Where are the first 2 types of linkages found?
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In membrane and secretory proteins.
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Where is O linkage of Xyl-Ser found?
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In proteoglycans
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What is the requirement of N-linked GlcNAc and Asn?
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-Must be linked to the sequence Asn-X-Ser/Thr
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What is the 1st step in Biosynthesis of N-linked sugars?
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Preassembly of an oligosacch. chain to Dolichol phosphate.
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What is dol-P?
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Dolichol phosphate; a membrane isoprenoid derivative.
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What is a major regulator of Dolichol phosphate synthesis?
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Cholesterol metabolism; Mevalonic acid is the precursor of both dol P and cholesterol.
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What is step 2 of N-glycosylation?
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Translation of proteins in RER
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What is step 3 of N-glycosylation?
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Oligosaccharyltransferase catalyzes the co-translational transfer of precursor oligosacch. chain from dol-P to the Asn residue.
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Where does the Asn residue hve to be located again?
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In the sequence Asn-X-Ser/Thr
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Where does step 3 occur?
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in the lumen of the ER.
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Where does the building up of the oligosaccharide precursor occur?
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-First 7 steps (2 glu + 5 Mannoses) on RER face
-Last 7 steps (4 more mannoses + 3 Glc) IN RER lumen |
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So what 2 different enzyme types are needed for N-linkage?
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-14 Glycosyltransferases - for making the precursor
-1 Oligosaccharyltransferase - to transfer precursor to Asn. |
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What happens after the actual N-linkage is made?
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Vesicular transport from RER lumen to golgi for processing and further modifications.
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What kind of modifications occur on the glycoproteins in golgi regions?
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Chaperones recognize specific sugars and assist in specific protein folding.
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Ok. Recap; where are O-glycosidic linkages between GalNAc and Ser/Thr found?
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In secretory and membrane glycoproteins.
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How is O-linked glycosylation different from N-linked?
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-No specific sequon recogn'n.
-No preformed precursor -No common core structure -Not cotranslational -Stepwise addition of sugars -No glycosidases |
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Where does each function:
-Glycosidases -Glycosyltransferases |
Glycosidases - ER and golgi
Glycosyltransferses - Golgi |
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How is o-linked glycosylation SIMILAR to n-linked?
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Both use the action of glycosyltransferases to make the oligosaccharide chain.
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What 2 types of O-linkages exist again?
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1. GalNAc - Ser/Thr
2. Xyl - Ser |
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Where are Xyl-Ser linkages found?
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In Proteoglycans
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What are proteoglycans?
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Glycoproteins that contain a spcf type of oligosaccharide called GAGs
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What are GAGs?
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Glycosaminoglycans - neg charged polysaccharides made of repeating disacch. units which are sulfated.
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How many GAGs are commonly found in Proteoglycans?
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MANY - like 100 or more
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What 4 GAGs are used in proteoglycans?
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-Hyaluronic acid
-Chondroitin sulfate -Heparin/heparin sulfate -Dermatan sulfate |
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How are GAGs attached to proteoglycans?
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Via covalent links - EXCEPT HYLAURONIC ACID
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What is the common linkage region for the GAGs except hylauronic acid?
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GlcUA-Gal-Gal-Xyl-Ser
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What is the purpose of Hyaluronic acid if not covalently linked to the proteoglycan?
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Serves as the backbone scaffold for proteoglycans.
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What is a proteoglycan macromolecule made of?
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Core - hylauronic acid
-Link proteins -GAGs bound to core protein |
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What are the functions of proteoglycans?
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-Bind H2O via highly neg charged sugars to support joints.
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