Lec 5 and 6: Proteins (Structure and Function) Flashcards
what are proteins?
Fundamental cellular component vital for all cellular functions
state the function and give an example for each protein type;
structural, storage, transport, hormonal, receptor, contractile, defensive, enzymatic
what is a polypeptide?
Amino acid monomers linked together by peptide bonds
what do more than 40 amino acids form?
a protein!!
how does the sequence of the amino acids effect the structure and therefore function of a protein?
- different sequence of amino acids
- dfferent primary structure
- different folding and coiling of the beta pleated sheet and coiling of the alpha helix
- different tertiary struture so the folding of the protein is different
- different different 3D shape, active site is different also
- substrate can not fit into the active site, enzyme no longer works
how many standard amino acids are there? what is the name given to these amino acids?
20
proteinogenic amino acids
which enantomer is more dominate?
L enantiomers
(D is very rare)
what happens to a zwitter ion when an acid or base is added?
in acid: the carboxyl group gains a hydrogen
in alkali: amino group loses an hydrogen
what type of physicochemical properties (4) can the R group on the amino acid be?
state how many out of the 20 are each of this property
Nonpolar (9) Hydrophobic (“water-hating”)
Polar (6)
Acidic (2)
Basic (3)
(polar, acidic and basic are hydrophillic)
which are the non polar amino acids?
glycine (Gly)
alanine (Ala)
valine (Val)
leucine (Leu)
isoluecine (Ile)
methionine (Met)
phenylalanine (Phe)
tryptophan (Trp)
prolive (Pro)
out of the non polar amino acids which one has a non chiral centre?
glycine
out of the non-polar amino acid which one is not a primary amino acid?
proline
which are the acidic amino acids?
at what pH are their sides chain negatively charged?
Aspartic acid (Asp)
Glutamic acid (Glu)
pH 7.4
which are the basic amino acids?
at what pH are their sides chains positively charged?
lysine (Lys)
Arganine (Arg)
Histindine (His)
which are the polar amino acids?
why are they polar?
Tyrosine (Tyr)
Asparagine (Asn)
Glutamine (Gln)
Serine (Ser)
Threonine (Thr)
Cysteine (Cys)
they are polar because they can form hydrogen bond interactions with similar side-chains and peptide bonds
which amino acid can join together to form a disulphide bridge?
cysteine in a oxidation reaction
how do amino acids link together and what bond does this form?
link at the carboxyl group of one amino a and an amino group of another amino a via dehydration synthesis
peptide bond is formed
what does it mean by proteins are directional?
they are labelled from n (amino) terminus to c (carboxyl) terminus
whay are cis amino acids rarer than trans?
which amino acid is an exception to this?
because the side chains are bulky if they are on the same side they clash and are less stable
glycine is an exception
what is the significance of proline in the secondary structure of a protein?
proline disrupts α-helix structure (“helix breaker”)
in which proteins are alpha helices most/least abundant in?
- Abundant in haemoglobin
- Absent in chymotrypsin (digestive enzyme)
what is meant by amphipathic?
has a hyrdophobic and hydrophillic parts
which is more flexible? alpha helices or beta pleated sheets?
b-sheeets more flexible because they have a greater distance between the amino acids
can beta pleated sheet to be amphiphatic?
yes they can
you have the plane of beta sheets and the above bed and below bed of side chains
what are loops and radom coils usually part of?
enzyme active site
what are structural motifs?
Arrangements of 2° structures (super-secondary structures) that occur frequently within a protein and can be associated with a specific biological function
what are the type of structural motifs (6)?
- β-Hairpin
– Helix-loop-helix
– Greek key
– Coiled coil
– Zinc finger
– Beta barrel
what is a β-Hairpin motif?
what is most common in?
= Two adjacent anti-parallel β strands joined by a hairpin loop
most common in globular proteins
what is a Helix-loop-helix motif?
what is it most common in and what is it’s function?
Helix-loop-helix motif
most common in;
transcription factors
cell signalling proteins
function:
DNA-binding
Ca2+-binding
what is a greek key motif?
what is it most common in?
Three anti-parallel β-strands connected by hairpins plus a 4th strand which is adjacent to the 1st and linked to the 3rd by a longer loop
Common in a range of proteins (e.g. proteases [trypsin], cytokines [TNFα])
what is a coiled coil motif?
give examples of proteins that contain this motif
Usually contain repeats of a 7 residue pattern (hxxhcxc) h=hydrophobic, c=charged, x=any
Resulting amphipathic α-helices have a “stripe” of hydrophobic residues that coil around similar stripes in other helices such that hydrophilic residues project outwards
Leu zippers in transcription factors [e.g. c-Fos] Structural proteins [Myosins]
what is a zin finger motif?
in which proteins is it most common?
what is its function?
=Two anti-parallel β-sheets followed by 1 α-helix, stabilised by a zinc ion
Common motif in many proteins including transcription factors Example: Kruppel-like factor 4 (KLF4)
Functions: Binding of DNA, RNA, lipid and protein substrates
what are beta barrel motifs?
what are the 4 type of beta barrel motifs?
what are they most common in?
Multiple anti-parallel β-sheets that twist and to form a closed structure
First strand is hydrogen bonded to the last
4 types:
Greek key barrel
Up-and-down barrel
Jelly roll barrel (complex)
Beta-helix barrel
most common in water channels (aqauporins)
what are domains and what are they formed from?
give an example
A polypeptide chain (or part of chain) that folds independently into a stable structure with its own hydrophobic core
Formed from several simple motifs and secondary structure elements
e.g Src homology 2 (SH2) domain – binds phospho-Tyr residues, important in insulin signalling
which bonds occur in the tertiary structure?
– Hydrogen bonds = Between R Groups
– Ionic bonds (=electrostatic attraction) = Between CO2- and NH3+ of R Groups
– Disulphide bridges (=covalent crosslinks) = Between cysteine –SH groups (Cys-S—S-Cys)
– Hydrophobic interactions = Hydrophobic R Groups cluster inside proteins to shield themselves from water
which linkage is the strongest in the tertiarty structure?
disulphide bridge
what are examples of fibrous proteins? what are the functions
fibrous proteins provide support and strength
Collagen
Keratins;
α-keratins – Mammalian hair and nails
β-keratins – Invertebrate silks, reptile scales, claws – Avian feathers, beaks and claws
are fibrous proteins insoluble or soluble in water
insoluble
what makes up collagen?
super helices of Gly-rich triple α-helices (=tropocollagen)
that assemble into fibrils
what is the function of collagen?
collagen is the main protein in connective tissure
so itsupports, connects or separates tissues and organs
what are α-Keratins made up of?
Composed of coiled-coils of two α-helices that assemble together into larger fibres
what are the properties of α-keratins?
Strong and inextensible
Insoluble and chemically inert
because Disulphide bridges cross link coiled-coils making it very stable also
what is an example of β-Keratins?
fibroin
what is fibroin?
what is it made up of and why is stretchy?
Fibroin is found in silk and spider webs
Layers of anti-parallel β-sheets rich in Ala and Gly residues
Sheets joined by amorphous stretches which confer elasticity and strength
what are globular proteins?
give examples
Mixture of irregularly folded 20 elements to form a compact 3-D shape
e.g
Myoglobin
Haemoglobin
Immunoglobulins
what describe the structure and function of haemoglobin
it is a tetramer
4 polypeptide chains/subunits (α2β2 = adult haemoglobin)
4 haem molecules (haem = porphyrin ring +Fe2+ , binds O2)
function: Transports O2 from lungs to the rest of the body Releases O2 to permit aerobic respiration to provide energy
what is myoglobin?
related to haemoglobin, exists as single polypeptide
what diseases are related to the mutation of haemoglobin genes?
Sickle cell disease:
caused by a “non-sense mutation = changes primary sequence”
– resulting in Change in RBC shape (sickle-shaped cells)
– RBCs rigid, become blocked in capillaries Ischaemia/Organ Damage/Pain
– Increased haemolysis (=RBC destruction) Anaemia/Spleen damage
Thalassaemias
what are immunoglobins?
what are they made up of?
Y-shaped proteins of the immune system which identify and combat invading foreign organisms
made up of:
4 chains linked by disulphide bridges
– 2 large H (heavy) chains
– 2 short L (light) chains
-disulphide bonds
variable region: form specific binding sites for non-self targets
constant region: acts as marker for other components of the immune system
what is meant by the denaturation of proteins?
Process in which proteins lose quaternary, tertiary and secondary structure present in their native state due to a change in environment
resulting in loss of function
how can pH cause denaturation?
explain what happens in low and high pH
Ionic bonds very sensitive to pH:
– Break ionic bonds
– Disrupts tertiary structure
– proteins become insoluble and precipitate out of water
Low pH:
high H+ conc
H+ + COO- —> COOH
High pH:
low H+ conc
NH3+ —> NH2 + H+
how does high temperature cause denaturation?
Increase in temp vibrates and breaks H and ionic bonds
proteins become insoluble and precipitate out of water
what is pyrexia?
increased body temperature (fever)
due to anti-viral defence mechanism
how do solvents cause denaturation?
which one specifically cause denaturation?
- Ethanol, acetone, phenol (organic solvents)
- Forms new H bonds with protein side chains and backbone
- Disrupt intra- and inter-chain H bonds
- Causes protein to unfold and denature
do solvents cause proteins to become insoluble?
no
because solvents dissolve the protein and renders it soluble
