6: Protein Fundamenals 2 Flashcards
what is post-translational modificaion of proteins?
covalent and enzymatic modification of proteins following protein biosynthesis (transcription and translation)
covalent - forming new covalent bond or cleaving existing bond (including peptide bond)
what is the significance of post-translational modification of proteins?
what happens to proteins after they’re made determines protein function
what can PTMs affect?
- stability
- localization
- inactivation
- activation
- interactions
- protein conformation
how does phosphorylation modify a protein?
attachment of phosphate to a serine, threonine, or tyrosine amino acid residue
- can promote or inhibit protein interactions
- kinases add phosphate
- phosphatases remove phosphate
impact of glycosylation on a protein
attaches a sugar group to an amino acid residue
- can promote protein stability and localization of proteins
how does lipidation modify a protein?
attaches a lipid group to an amino acid residue
- lipidation can target proteins to membranes by acting like membrane anchors
how does acetylation/methylation modify a protein?
alters charge or provides a binding site for other proteins
- important in regulation of histones (chromatin)
how does ubiquitination modify a protein?
addition of ubiquitin protein to a lysine residue
- targets protein for degradation (destruction)
how/why are there so many more protein species in the cell than encoded in the genome?
one gene can give rise to a series of related proteins
how?
- alternative splicing of mRNAs
- post translational modifications (PTMs)
- specific proteolysis
what is proteolysis?
enzymatic process that produces two or more peptides from one protein (breaks apart)
- allows different parts to the protein to have differential localization and function (each section has a different function)
what is the effect of a conformational change?
a conformational change is when proteins change their shape in response to environment or other factors
(each different protein shape is a different conformation)
- affects protein interactions with other molecules
conformational change: effect of phosphorylation-induced change
protein structure changes from bent to extended conformation through phosphorylation –> causes activity (DNA binding)
- can make some proteins inactive and some active
conformational change: effect of ligand-induced change
binding of heme to a protein causes conformational change in protein
Ex. formation of an alpha helix (without ligand binding, there is a loop instead)
what are conformational changes caused by?
- post-translational modification
- substrate/ligand binding
- electrochemical changes
how are membrane proteins associated with the cell membrane?
N and C terminus can be in either intracellular and extracellular
- integral (thru the whole membrane) or peripheral (anchored)
characteristics of transmembrane domains
- typically alpha helices
- contain about 20 amino acid residues
- hydrophobic
what are the two types of membrane insertion of a transmembrane protein?
1) polypeptide has a terminal ER signal sequence and an internal stop-transfer sequence.
- ER signal sequence attaches the polypeptide to the membrane. The polypeptide migrates into the lumen.
- stop-transfer sequence stops the movement of the polypeptide towards the ER lumen
2) polypeptide only has an internal start-transfer sequence.
- start-transfer sequence is not on the end of the polypeptide
- everything after the start-transfer sequence gets moved into the lumen of the ER.
transmembrane proteins: G-Protein Coupled Receptors (GPCRs)
Explain what they are and what they do.
- the most important widespread receptor in the cell: has many functions (many transmembrane domains)
- ligand binding domain –> extracellular
- enzymatic binding is intracellular
- function: interacts with other proteins and signals what happens when a ligand binds
- how? ligand will bind, GPCR will shift and change conformation, it will do something cytoplasmically, and then something happens inside the cell.
transmembrane proteins: ion channels
explain what they are and what they do
- central pore is formed by tetramers/monomers with 4 domains.
- ligands can bind on extra or intracellular side, or not at all
- the amino acids that line the pore determine selectivity and controls which ions can pass through the pore
transmembrane proteins: voltage-gated ion channels
explain what they are and what they do
- changes in voltage open/close an ion channel (or the “gate” at the bottom of the channel)
- triggered by differences in voltage across the membrane
transmembrane proteins: transporters
explain what they are and what they do
- similar to ion channels but move larger molecules (like drugs)
- mostly present as dimers (two of the same molecule linked together)
how does an ABC transporter work?
- ATP binding cassette (ABC) transporters have a region that binds ATP and a substrate
- uses ATP energy to transport drugs in and out of the cell
what are the major protein classes as drug targets?
- GPCR
- transporter
- ion channel
- enzymes
- transcription factors
- tubulin
