Module 1: From Polypeptide to Protein Flashcards
Polypeptide
primary structure of the protein comprised of a linear array of amino acids
What are the two ends of a polypeptide?
Amino end (N-terminus) and Carboxyl end (C-terminus)
Parts of an amino acid. Which of these parts make the amino acids unqiue?
Hydrogen atom, carboxyl group, amino group and R group. R group is what gives the amino acids its unique properties
Two ways in which amino acids are classified?
solubility in water & polarity of side chain
Solubility
refers to a physical property of a molecule that can bond with water through HB
Hydrophillic
solube; HB can form with water; charge-polarized
Hydrophobic
insoluble; HB cannot form with water; water repels HB in favour of forming bonds with itself
Two catergories of hydrophobic amino acids
aromatic amino acids and aliphatic amino acids
Which amino acid can act as an aromatic amino acid and an aliphatic amino acid?
tyrosine
Prime contributors to overall charge of protein
postively charged (lysine and arginine) and negatively charged (aspartic acid and glutamic acid)
Cysteine
can form covalent bonds with other cysteine residues forming disulphide bridges
Glycine
very small and can allow bends in polypeptides
Proline
side chain can form bond back with amine sidechain of amino acid producing a kink in the chain
Histidine
has a sidechain that allows it to shift from positive to neutral charge depending on pH of the environment
Peptide bonds
formed by condensation reactions (-water) between the amino group of one amino acid and the carboxyl group of another amino acid
mRNA
carries gene’s message from DNA out of nuclues to a ribosome for production of a specific protein this gene codes for
Primary structure of protein
linear arrangement of amino acid and the sequence is determined by nucleotide sequence of encoding gene
double stranded DNA is transcribed into single stranded mRNA, once its introns are removed it becomes a mature RNA containing only the codons for that specific protein, and then it is a translated in a ribosome
Statistical coil
idea that proteins may not have a single, stable structure but rather switch between a collection of related structures
local interactions that maintain protein shape
ionic bonds, hydrogen bonds, van der Waal forces, hydrophobic effect
Secondary structure of a protein
consists of local chemical interactions that fold a protein
Motifs
combinations of secondary structures
three basic secondary structures
alpha-helix, beta sheet, and turn loops
alpha helix
sprial, rod-like structures
beta sheet
planar structure, composed of alignments of two or more strands
turns/loops
connectors; bends in the polypeptide backbone that lie between the alpha helcies and beta strands
Coiled-coil motif
two alpha helices are wrapped around one another
favoured in the cytosol
zinc-finger motif
alpha helix and two beta strands held in position by interaction of precisely position Cys and His residues with a zinc atom
usually found within DNA binding proteins
beta-barrel motif
large beta-sheet that loops back around itself
first strand and last strand of sheet forms HBs with each other
useful for forming a channel or pore across hydrophobic membrane
helix-loop-helix motif
two small alpha helicies joined but are held together in specific orientation relative to one another by noncovalent interactions between specific amino acid residues and a cofactor, calcium
Tertiary structure of protein
overall 3D confirmation of single protein
fundamental unit of tertiary structure is the domain
Domain
substructure produced by any part of a polypeptide chain that can fold independently into a compact, stable structure
two types of domain
functional and structural
Functional domain
regions of protein that perform a specific activity
Structural domain
regions of protein that form compact, largely independent globular domains
Quaternary structure of a protein
number and organization of subunits in a multimeric protein
Intrinsically unstructured proteins
proteins that lack a tertiary structure as isolated subunits
when they interact with one another they may form a structured complex
Native state
refers to the most thermodynamically stable conformation of a protein
Reversible denaturation experiment
Christian Anfinsen used denaturation and dialysis to unfold the protein and bring it back to its native state. He used urea and beta mercaptoethanol to unfold the protein. It was observed that as soon as it was brought back to its native state, it reassembled spontaneously into its folded condition.
Sickle cell anemia
occurs due to misfolded haemoglobin
there is a single amino acid change in beta-globin sequence from glutamine to valine at position 6.
Emphysema
condition when individual has diffculty breathing
alpha-1-antitrypsin -> protein found in lungs to maintain elasticity of the tissue
aspatic acid is replaced with valine at position 256
What are prion diseases?
fatal transmissable neurodegenerative diseases.
it has a lengthy incubutation period in which it has a compromised immune system preventing the cells from notifying the body that something wrong is taking place
modes of acquisition for prion disease
spontaneous, heritability, infectious
Prion
abnormal form of a normal prion protein (PrPc is the normal form, and the PrPSc)
Charactersitics of normal vs. abnormal prion protein
rich in alpha helicies vs. rich in beta sheets
soluble vs. insoluble
PK sensitive vs. PK insensitive
no aggregation vs. aggregation
What gene codes for prion protein?
PRNP gene is located on the short arm of chromosome 20
Missense mutations
changes in single amino acids
insertions or deletions
insertions or deletions of additional amino acids
nonsense mutations
truncated forms of proteins
What are the clinical features of prion disease?
progressive neurological decline (rapidly progressive dementia, ataxia, visual problems, akinetic mutism)
What is the suspected method of infection in prion proteins?
It is easier for the PrPSc to infect the PrPc when it is in its transient unfolded state (more suspectible to transitioning into abnormal prion)
then these PrPSc clump together through nucleation to form amyloid fibrils which then breaks out multiple seeds that can go on coverting PrPc into PrPSc
Where does the infection of PrPc occur?
usually occurs in ER, but can also occur in lysosomes and endosomes
What technique can be used to observe the conversion of prion proteins in the body?
immunofluorscence
Are prion aggregates always bad?
No, Mod5 is a yeast prion that takes advantage of aggregation and uses it during stressful situations
