BC 19 PTM Flashcards
PTM required assembly
1 Folding
2 covalent modification
3 binding
some of these need PTM to occur, not mutually exclusive
Folding
Chaperones
- proteins usually fold so hydrophobic cores are at center, awary from water
- presence of hydrophobic molecules on outside lets chaperone know it is unfolded
- bind to small stretches of hydrophobinc AA to initiate or correct protein folding
assisted by HEat Shock Protiens HSP
-chaperones are catalyst, that assemble without being part of assembly
HSP 70
-recruited, bind to stabilize unfolded/misfolded form, DURING translation
-uses ATP for correct folding, required
-cannot fold, give to proteasome machinery for burn
Signal Sequences
delivery to a specific organelle
n terminus or c terminus
or protein folding can bring AA together that create a signal patch
advantave of sequence vs patch it can be removed easily at destination
ER signal sequence-first use of a signal sequence occurs while protein is still being translated
-cotranslational instertion
-recruitment of ribosomes to ER surface is by Signal recognition particle (SRP): recognizes and binds SS
SRP receptor: within ER membrane binds SRP
GTP HYDROLYSIS REQUIRED
LOOK AT IMAGE
Phosphorylation
most wide spread and reversible PTM
addition of phosphate group to serine threonine or tyrosine
presence or abses of single phosphate froup on key reg protein determins cancer or no
T286 mutation in cyclin D1, phosphorylation normally exports to nucleus, and subsequent to cytoplasm, loss of phosphorylation causes accumulation in nucleus, in esophageal cencer and increases onco potention
Acetylation
HATS: loosen chromatin
-acylated makes it looser, hyperacylated competent for transcription and recombination
HDAC: tighten chromatin
methylation
transfer of one carbon methyl group to a substrate,
-methyltransferases
SAMe (s-adenosylmethionine) primary methy group donor
- occurs so much SAM super useful substrate
- gene regulation, histone methylation regulates DNA availability
- mono-di-tri methylation
Disulfide Bonds
protein Disulfide isomerase (PDI)
assist to form DiS between two cysteine residues (assists doing them correctly)
located only in ER, can only occur in ER
N linked Glycosylation
Most common glycosylation
addition of sugars (N linked- Aspargine (N)) NOT N TERMINUS
-can be large branched glycan, begins in cytosol with two n acetyl glucosamine sugars, modifying reside in ER and golgi
O linked glycosylation
takes place in lumen of Golgi
covalent addition of n-acetyl galactosamine to OH croup of either serine or threonine
only ONE SUGAR AT A TIME no branched chains
on mucin protiens, and PG of ECM
Carboxylation
PTM of glutamate to gamme carboxyglutamate
- blood clotting cascade
- each unaltered glutamate has one negatively charged carbonyl group COO-, but after carboxylation reaction, it has two
- calcium binds to carboxyglutamate and bring these factors to the negatively charged platelet surface
Ubiquitination
Rapid proteolysis by Ubiquitin (Ub)
76 AA polypeptide
covalently attached to lysine residues of the tarted protein by ubiquitin ligase
Ub molecule can also be covalently attached to eachother forming chains ultimately binding to single lysine residue
Ubiquitination use to degrade misfolded protiens and can be used for degredation
polu Ub sent to proteasome
Ub pathway
E1, E2, E3
- Activation of Ub by being attached to E1
- E1(Ub activating enzyme) binds to Ub donates activated Ub to E2
- E2 (Ub conjugating enzyme) catalyzes covalent addition of Ub to Protien substrates
- E3 (Ub accessory protein) confers specificity, to Ub allows binding of substrates but does not actually catalyze transfer of Ub
- E2E3 complex togher called ubiquitin ligase
Proteasome
Ub proteins degraded by ATP dependent multiprotien subunit called proteasome
barrel shaped complex binds, unfold and threds linear PP into protein core at center
digested into peptides
Ind ubiquitin molecules are released intact and reused
Hypoxia
low O2 pathological condition
O2 sensed by kidney
kidney secretes EPO which stim the prod of RBCs in BM
controlled by PTM of hypoxia induced factor 1 HIF1
HIF1alpha
O2 sensing is possible by O2 dependant ubiquitination of TF HIF1alpha.
HIF1alpha is a substrate for cytoplasmic enzyme prolyl hydroxylase
Proline hydroxylation of HIF1alpha requires O2. Once the proline residues are dydoxylated the protein con be recognized by E3 component of Ub Ligase that targets it for degredation by lysosome.
Under low O2 PH cannot function and hydroxyproline residues not created. E3 connot bind
HIF1alpha translocated to nucleas where with HIF1beta it can increase the expression of a number of hypoxia related genes including EPO
the kid is then able to synth EPO to return O2 levels and HIF1alpha degraded again
