Protein Modification Flashcards
T & B Cells
T cells recognize antigen and attach infected cells, killin the cells and the virus within
T cells also activate B cells which are memory cells (remember invading agents, remember the shape of the proteins on cell wall). They produce antibodies that bind to the antigens
Antibodies
Proteins with high specificity for ligands- protein binding specificity
Antibodies (immunoglobulin) are proteins produced by the immune system, bind to antigen
Antigen: foreign substance that elicits production of an antibody
In some cases antibody can distinguish between proteins that differ by a single amino acid
Antibody structure
- Antibody has 4 subunits(polypeptides: 2 heavy & 2 light chains
- Chains are held together by S‐S bonds
• Each
polypeptide
chain
can
be
divided
into
2
domains:
– Variable
domain
VL
&
VH
– Constant
domain
CL
&CH
• the variable domains interact with the antigen- Variable sites are on the tips. Every antibody has a different variable region. A lot of beta pleated sheets
The binding site is where the variable regions for the heavy and the light regions come together
Influenza Virus
Proteins protruding from the virus (hemagglutinin), binding site and transmembrane region
CDR
The variable domains contain the complementarity‐determining region (CDR)
CDR contains 6 highly variable loops that form the antigen binding sites, interacts with antigen
Epitope
Epitope: region of antigen that is recognized by the antibody
Interaction between antibody and epitope of antigen is complimentary
Fits like a glove
Antivenom
Inject horse with genome, they generate antibodies to combat the venom. Those antibodies are removed and put into humans. Not possible to be completely purified so its possible that the human would get sicker
Protein folding
When proteins are first being translated they can be “sticky”- Energetically unstable- hydrophobic patches that are exposed
Sometimes proteins denature, but can denature with help of other proteins
The role of molecular chaperones
Facilitate proper folding in the cell
Bind and stabilize partially or unfold proteins and prevent interactions with other proteins
Ex: mRNA, chaperone hsp70 either folds into a native polypeptide or puts in in chaperonin hsp60 which folds it into its native state. Then release into the cytosol
Chaperonins
Multiple of the same subunits. Hsp10 (groES) makes the cap, 60 (groEL)makes the two barrels
Substrate goes into substrate binding cavity
Uses 14 ATP- 7 to bring it in, 7 to eject i
15 seconds
Types of Protein modifications
Often essential for the function of a proteinase the regulation of protein activities
Different modifications: Methylation acetylation Phosphorylation Hydroxylation Ubiquitination Glycosylation Proteolitic processing Disulfide bond formation, and cleavage
Protein modification
Amino acids often modified after translation
Modification can affect regulatory function
Can affect structural features
Methylation
Addition of methyl group
Regulation of gene expression
Acetylation
Affects about 80 percent of all proteins
Done by N- acetyltransferases
Transfers the acetyl groups from acetyl CoA
Important in gene regulation
Protein phosphorylation
Addition of a phosphate group to the hydroxyl of serine, threonine, or tyrosine (sometimes histidine)
Phosphorylation/dephosphorylation (kinase/phosphatase) provides a quick mechanism for alterin protein activity
How many modifications per protein?
Not limited to one
Ex: Histone octamer. Some things can be methylated phosphorylated etc
Hydroxylation
Hydroxyl groups can be added to lysine or proline
Glycosylation
Often occurs in ER(further modification in the Golgi) found in secrete proteins or those on the outside of the cell
Addition of carbohydrates can be added to Asn, Ser, or Thr
Adding a lipid group
A protein may be anchored to the membrane if it is attached with lipid molecules such as farnesyl group, palmitate, or myristate groups
Integral proteins anchored by lipid groups
Proteolytic processing
Removal by protease- reducing environment
Activation and transportation
Seen commonly in proteins that’s are in response to conditions (hormones), in response to a region (proteases), or transported to mitochondria and chloroplasts. this requires the removal of the signal peptide
Removal of n terminal methionine
Proteolytic cleavage to activate a protein
Many proteins are synthesized as larger precursors that need to be cleaved to become active
Ex: chymotrypsinogen is synthesized in the pancreas and the secreted into the small intestine
Become active enzyme chymotripsin after trypsin cleaves its proform
Uniquitination
Proteins marked for degradation linked covalently to ubiquitin
Brings it into the proteosome which breaks it down
Proteolysis
Hydrolysis process in which peptide bonds of protein is cleaved into small peptides or individual AA
Why are proteins degraded?
- no longer needed by the cell
- Proteins are damaged
- misfolded protein
- too much energy to repair a damaged/misfolded protein
