Term
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Definition
1)The majority of proteins contain covalently attached molecules
(i.e., proteins contain more than just amino acids)
2)>200 different amino acids have been found in proteins (20 amino acids coded in the genome)
3)Modifications are a mechanism to increase the functional diversity of a limited gene pool (~20,000 genes in the human genome) |
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Term
| Protein Phosphorylation Docking Signaling |
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Definition
-Phosphorylation typically effects Ser, Tyr, and Thr AAs.
1)Ligand (Growth Factor) binds to Tyr-Kinase receptor (HER2)
2)Stimulates Try Kinase activity, leads to phosphorylation of tail of receptor
3)Creates docking point for SH2 (e.g.: Grb2) along with signaling protein --> allows for cascade of protein and additional signaling (e.g.: Ras).
Phosphorylation also involved in 1)enzyme activation/inactivation 2)modulation of molecular interactions |
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Term
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Definition
| Very specific inhibitor of the ABL kinase in Philadelphia chromosome where there is a reciprocal translation between the 9th and 22nd chromosome resulting in a fusion of the BRC-22q11 and ABL-2q34 gene where ABL is constitutively active causing acute lymphoblastic leukemias. |
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Term
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Definition
1)Two types: N-linked (Asn) and O-linked (Ser and Thr).
2)Estimated that 50% of the ~25,000 genes in the human genome encode proteins that undergo glycosylation.
3)O-linked: Simple covalent modification; collagen & glycophorin.
4)N-linked: More complex, branched, step-wise. Initiated in ER, *BACKBONE BUILT ON DOLICHOL PHOSPHATE AND YOU WANT TO FORM A DOLICHOL POLYISOPRENOID.* Goes from ER to Golgi then plasma membrane. Addition of more carbohydrates occur in ER to golgi transportation.
-Carbohydrates determine where protein will end up. For instance if a O antigen undergoes GalNAc transferase, you'll get a A antigen, if it undergoes Gal transferase, you'll get a B antigen. |
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Term
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Definition
Covalent attachment of Ub to proteins is an ATP-dependent process involving 3 enzymes, E1 (1 gene, nuclear & cytoplasmic isoforms) *activation event, requires ATP*, E2 (~10-20 genes) [through thioester intermediates], E3 (>100 genes) *E3 is specific!*
Also different types of Ubiquitination and hence, difference functions.
Linkage of Ub is through isopeptide bond
between ε-amino groups of a Lys residue.
For example
1)Mono-Ub-->Movement of protein
2)Multi-Ub-->Endocytosis
3)Poly-Ub K63 --> DNA repair, endocytosis, activation of protein kinase
4)Poly-Ub K48 --> Degradation
26S subunit. |
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Term
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Definition
1.Reversible (ADP ribosyltransferases and hydrolases)
2.Negatively charged phosphate groups
3.Bacterial toxins, such as diphtheria, cholera, and pertussis toxins act by modifying crucial host cell proteins such as heterotrimeric G proteins, actin, and elongation factor-2 (EF-2), resulting in activation or inactivation of the cell functions modulated by these protein substrates. The mono-ADP-ribosylation reactions induced by these bacterial toxins are a crucial part of the pathogenic mechanism that cause these diseases. |
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Term
| Hydrophobic PostTranslationalModifications |
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Definition
1.Fatty acids (Myristate C14; Palmitate C16)
2.Glycosyl Phosphatidylinosito (GPI)
3.Prenylation (Farnesyl C15; Geranylgeranyl C20)
4.Cholesterol
5.Effects = membrane association |
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Term
| Glycosyl Phosphatidylinositol (GPI) |
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Definition
A. Post-translational modification, occurs in ER by the action of a transamidase complex. *anchors to lumen of ER, ends up extra-cellular portion on the plasma membrane*
B. Requires 20-30 predominantly hydrophobic aa at the C-terminus. This hydrophobic region is removed during GPI addition.
C. “Anchors” proteins in the outer leaflet of the plasma membrane. Allows targeting to specialized regions of the plasma membrane (caveolae, rafts).
D. Phospholipases can cleave GPI which can lead to the release of GPI anchored proteins from the membrane.
*reversible* |
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Term
| Farnesylation (C15) / prenylation |
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Definition
1)Post-translational modification
2)Requires CAAX consensus sequences at the C-terminus (C = cysteine, A = aliphatic amino acid, X = any amino acid
3)Processing reactions include:
a) Farnesylation of cysteine
b) Proteolytic removal of AAX, resulting in cysteine at the C-terminus of the protein
c) Carboxy-methylation of cysteine
4)Promotes interaction of the protein with the membrane
Ras
5)Farnesylation of Ras is required for its association with the plasma membrane, its functioning in signal
transduction, and is essential for the transforming activity of oncogenic variants of Ras. Protein farnesyltransferase (FTase) is a target for anticancer therapeutics:
a)inhibitors of FTase: caused tumor regression in H-Ras transformed mice; in clinical trials for the treatment of human cancer.
-2 farnesyl groups (C15 + C15) form the precursor to cholesterol. |
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Term
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Definition
| Covalent attachment of cholesterol to secreted morphogens such as Hedgehog and Wnt. Involved in developmental patterning of the head and brain, as well as cancer. This is consistent with previous observations that inhibition of cholesterol synthesis results in developmental abnormalities. |
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Term
| Sonic Hedgehog Processing |
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Definition
1)Comprised of
a)Signal Sequence
b)Signaling Domain
c)Autoprocessing domain
2)Fully processed SHH-N is comprised of a)Palmitate modification
b)Signaling Domain
c)Cholesterol Tail
-involved in bilateral eye & cranial/facial development. |
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