Protein Structure & Function Flashcards
Define the secondary structure of a protein, contrast the different types, and state what bonds are present.
Local spatial arrangement of polypeptide backbone (side chains NOT involved)
ALPHA HELIX = right-handed, C=O group bonded to N-H group of reside 4 amino acids away.
Intra-chain hydrogen bonds
Small hydrophobic residues = strong helix formers
Large bulky side chains/Proline/Glycine = helix breakers
BETA SHEETS = parallel or antiparallel (R groups alternate)
Inter-chain hydrogen bonds (more staggered when parallel)
Define the primary structure of a protein and state what bonds are present.
Linear amino acid sequence of polypeptide chain.
Peptide bonds (covalent)
Define the tertiary structure of a protein, contrast the different types, and state what bonds are present.
3D arrangement of all atoms in polypeptide (side chains included)
Covalent bonds = disulfide bridges
Non-covalent bonds = hydrogen bonds, ionic interactions, hydrophobic interactions, Van der Waals’
GLOBULAR = compact shape e.g. haemoglobin
Several types of secondary structure
Catalysis & regulation (enzymes)
FIBROUS = long strands or sheets e.g. collagen
Single type of secondary structure (high tensile strength)
Support, shape, & protection (structural proteins)
What are the supersecondary structural elements in the tertiary structure?
MOTIFS = folding patterns containing one or more elements of secondary structure
e.g. beta-barrel
DOMAINS = part of a polypeptide chain that folds into a distinct shape (therefore often has a specific function)
Define the quaternary structure and give some examples of quaternary proteins.
3D arrangement of protein subunits
i.e. more than one subunit present
e. g. haemoglobin (2 alpha, 2 beta chains)
e. g. ribosome (55 protein subunits + 3 RNA molecules)
What determines/assists protein folding?
Determined by primary structure (i.e. NOT random)
May have localised folding first which drives later folding.
CHAPERONE PROTEINS = catalysts/keep protein unfolded during synthesis to ensure correct folding/protect proteins as they fold
Give an example of a disease caused by misfolding of proteins. What is the mechanism of the disease?
Altered conformation of protein -> normally soluble proteins aggregate/tagged and degraded (abnormal proteolytic cleavage)
e.g. alpha helices -> beta-sheets
AMYLOIDOSES = accumulation of amyloid fibres (lots of beta sheets; precipitate, therefore are deposited in extracellular spaces, disrupts normal function)
e. g. Alzheimer’s (beta-plaque formed by abnormal proteolytic cleavage -> neurotoxic -> cognitive impairment)
e. g. Creutzfeld-Jakob disease (prion disease; abnormal proteins resistant to degradation -> insoluble aggregates of fibrils)
What are the differences in structure and function of haemoglobin and myoglobin?
Structure:
Haemoglobin = two alpha chains & two beta chains (tetramer)
Myoglobin = single polypeptide chain (75% alpha-helical)
Reaction kinetics:
Haemoglobin = sigmoidal O2 binding curve (more sensitive to changes in [O2]) (Cooperative binding)
Myoglobin = hyperbolic O2 binding curve
Regulation of O2 binding:
Haemoglobin = 2,3 - bisphosphoglycerate lowers O2 binding affinity (shifts curve to the right); affected by Bohr effect
Myoglobin = 2,3-BPG does not bind; unaffected by Bohr effect
Describe the mechanism of cooperative binding.
Binding of one oxygen molecule promotes the binding of subsequent oxygen molecules
Describe the Bohr Effect.
The effect of decreased pH and increased pCO2 on the O2 binding affinity of haemoglobin.
Increased CO2 at respiring tissues
(carbonic anhydrase) spontaneous CO2 + H2O ---------------> H2CO3 ----------> HCO3- + H+
HbO2 + H+ ———> HbH + O2
Binding curve shifts to the right
Maximised by BPG, low pH, increase in temperature
What is the effect of 2,3-BPG on haemoglobin? How does it cause this effect?
BPG binds to deoxyhaemoglobin but not oxyhaemoglobin
Stabilises T conformation/lowers binding affinity/shifts curve to right
Binds in the centre of the haemoglobin. Forms ionic bonds with +ve aa
What are the effects carbon monoxide on haemoglobin & myoglobin?
CO binds irreversibly to Fe2+ of haemoglobin & myoglobin.
Blocks O2 binding
Haem binding affinity: CO > O2
Increases binding affinity for O2, so less O2 released at tissues
(shifts curve to left)
COHb > 50% sat. = FATAL
Note: anaemic individuals more at risk of death due to CO poisoning (less free Hb available for O2 binding)
What is the difference between HbF and HbA? Why is HbF necessary for foetuses?
HbF has a higher O2 binding affinity. Needed for transfer of O2 to foetal blood supply across placenta.
Describe the clinical features of thalassaemias and the different types.
Imbalance between no. of alpha and beta chains in haemoglobin.
alpha-thalassaemia = decreased/absent alpha-globin production
1 absent = silent carrier
2 absent = alpha-thalassaemia trait (mild-severe symptoms)
3 absent = haemoglobin H (severe symptoms)
4 absent = hydrops fetalis (fatal)
beta-thalassaemias = decreased/absent beta-globin production
1 absent = beta-thalassaemia minor
2 absent = beta-thalsasaemia major
note: onset after birth
