S3- Proteins Flashcards
What is collagen?
Major structural protein (25% of total body’s protein) in the extra cellular matrix, resilient sheets to support skin and internal organs, molecular cables for tendons, bones and teeth
Bones and teeth are made by adding….to collagen
Hydroxy-apatite crystals (dash for pronunciation)
What is the primary structure of collagen protein?
Repeated sequence of 3 amino acids: Glycine-X-Y-Gly-X-Y
Forming a secondary alpha chain
The X and Y amino acids in the collagen primary structure are frequently…..
Proline and it’s modified version hyrdoxyproline
The 3 levels of collagen structure are…
Triple helix= 3 alpha chains
Collagen fibrils= cross-linking
Collagen fibre= packing
There are at least…types of collagen and have different…and different alpha chains combinations therefore…
12
Functions
Quaternary structure
The most common types of collagen are….and they form long….
(Fibril-forming collagen)
I, II, III
long fibrils (fibril-forming)
Type I collagen is..% of total collagen and is the main component of….
It is found in….,…,…but not in….
It is used in….
90%
Bone
Skin, hair, tissue
Cartilage
Tissue repair
Type II collagen is the main component of….and is found in the…..and…
Cartilage
Cornea
Vitreous humour
Type III collagen combines with type….and it’s found in…with…properties/ hollow organs such as…..
Type I
Tissues
Elastic
Skin, arteries, muscle, lungs, intestine (organs that stretch)
(Network forming collagen)
Type IV and VI collagen form a….which is important in the…..
2-dimensional matrix
Basal lamina (epithelial cells)
The specialised cells that make collagen (according to their location in the body) are called….
Fibroblasts = encode different alpha chains that will form different collagen molecules
Collagen mRNA goes from nucleus to RER, then Golgi then exocytosis to leave cell, what are the 6 steps of collagen production?
In RER = preprocollagen
1. Pro alpha chain backbone (Gly-X-Y)
2. Hydroxylation of proline and lysine (requires vitamin C)
3. Glycosylation
Procollagen (triple helix structure)
4. Exocytosis
Outside cell (the ends of the chains are still not wrapped around each other- so they just get cut later)
5. Cleavage of procollagen C and N terminals = form tropocollagen
6. Formation of cross-links (stabilised by lysyl oxidase)- copper dependent
Hydroxylation of proline and lysine forms…and the enzymes….are used
The reaction requires….to assist addition of oxygen from our diet
Hydroxyproline and hydroxylysine
Prolyl hydroylase and lysyl hydroxylase
Vitamin C
Proline hydroxy: stability of….due to extra…
Lysine hydroxy: stability of the…due to extra….
Triple helix, H bonds
Fibrils, cross linking
The cross linking of collagen uses the enzyme….which uses….as a cofactor
Lysyl oxidase
Copper
Extracellular matrix collagen have no….in fibril but rather very…layers to allow soft tissues (unlike bones and teeth)
Crosslink
Loose
What happens to collagen in old age?
- more cross0linking= more brittle and less elastic
- synthesis decreases
- bones more easily broken (brittle)
- arteries and skin less elastic
Aging or disease causes….which harms the damages the tissues and its functions
Fibrosis (thick/ stiff tissue scarring/ over-growth/ hardening and is attributed to excess deposition of extracellular matrix components like collagen)
Collagen is one of the….in fibrotic tissues
Upregulated genes (increased rate)
4 pathologies of collagen are:
- Osteogenesis imperfecta= mutations in collagen chains
- Scurvy= lack of vitamin c in diet= less hydrocylation
- Menke’s disease= copper deficiency
- Ehlers-Danlos syndrome type VI= lysyl oxidation deficiency
Osteogenesis imperfecta in known as….
It is caused by….(no family history/ genetic disorder)
Its severity increases with ….
Sometimes it is mistaken for….
Brittle bone disease
Spontaneous mutation
Substitution by large and charged amino acids (they prevent triple helix forming tight/ stable/ sturdy structure= loose= bones easily broken)
Child abuse
Osteogenesis imperfecta types, protein, defect, phenotype, sclera, life-expectancy
Type I= alpha 1 collagen/ collagen quantity/ mild non-deforming/ blue/ normal age
Type II= alpha1 and 2/ collagen structure/ perinatal lethal/ blue/ perinatal
Type III= 1and2/ collagen structure/ progressively deforming/ blue than normal/ childhood
Type IV= 1and2/ collagen structure/ moderately deforming/ normal eyes/ slight reduction in age
Scurvy is triggered by lack of…(vit C) which prevents….
Therefore collagen is not stabalised (less H bonds between alpha chains and less cross-linking)
Ascorbic acid
The enzyme activity of proline and lysyl hydroxylases
The main symptoms of scurvy are….
Around 200 cases of death in UK in 2022 due to….
Loss of teeth and easy bruising (lack of collagen to repair wear and tear by everyday activities)
Malnourishment
Menke’s disease are….and…
They are caused due to mutation in a….
Without treatment, life expectancy is…
Rare and X-linked
Copper transporter
3 years
Ehlers-Danlos has more than…types due to mutations in at least 20 genes found
Many of these genes are responsible for making collagen, others make….
20
Proteins that process, fold, or interact with collagen
Collagen has 3…handed helix chains that have…residues per turn
These combine to form…handed triple helix
Left
3.3
Right
In collagen helix structure, proline and hydroxyproline are on the….to max….
Small…residues are packed into the…
Outside, hydrogen bonds
Glycine, centre
Collagen 1 is made of 2….chains and 1….chain
Alpha 1
Alpha 2
Oxygen is….in blood and needs a transport system
….is for O2 and CO2 transport
….is for O2 storage
Sparingly soluble in blood
Haemoglobin
Myoglobin
Haemoglobin is the…that makes blood red
Its composed of 4….and 2…and 2…
Oxygen binds….
Protein
Protein chains
Alpha and beta (each has haem group with iron atom)
Reversibly
Haem is male of…
Fe2+ and proto-porphyrin IX
Hb chain has very similar….to Mb but differs at…of amino acid residues
3D structure
83%
Oxygen binding…tertiary and quaternary structure of Hb because binding to one subunit affects…with other subunits, which makes binding of next O2….
Alters
Interactions
Easier
Mb has greater…for O2 than Hb, so its good for….
Affinity (binding)
Storage function
Binding of O2 to Hb is….and the binding curve is…
Co-operative
Sigmoidal (s shaped)
Haem enables transport of other molecules like:…
Nitric oxide, carbon monoxide
Nitric oxide affects…which…
It binds to specific…and…
Walls of blood vessels= relax/ vasodilation= reduce blood pressure
Cysteine residues in Hb and Fe in haem group
Carbon monoxide is a…which binds…to haem
It causes…deaths each year
Symptoms include:…
Toxic gas
Irreversibly (better than O2)
60
Nausea, dizziness, confusion
Structure of amino acid?
Basic amino acid has….
Acidic amino acid has….
At neutral pH they exist as…
The nature of amino acid side chain/ R group determines…
Amine/ amino group NH2- carbon+H+R group- carboxyl group COOH
NH3+ (accepts H+= basic)
O- (donates H+= acidic)
Zwitterion
Its properties
The 4 types of amino acid groups are…
- Electrically charged side chains (acidic and basic)
- Polar uncharged side chains
3.special cases - Hydrophobic side chains
Peptide is….linked by…
The bond is…
1+ amino acids
Peptide bond/ amide bond
Very chemically stable/ planar (between HN and O)
Each amino acid unit on polypeptide is called…
Residue
Primary structure is…
It defines how the protein will…
Single change in amino acid structure can cause…
Linear sequence of amino acids
Fold and function
Disease
Secondary structure of protein has…and forms….such as….and…
H bonds
Stable structural elements
Alpha helix
Beta sheets
What determines the possible confirmations/ shapes/ structure of polypeptides?
Bond length and bond angle
Alpha helix has a…structure with….bonds
…residues per turn
Coiled
Intrachain H bonds (within a chain)
3.6
Beta sheets are stabilised by….
The chains can…by making…
Hydrogen binds between strands
Change direction
Reverse turns and loops
To function, proteins….to form a…structure
They create a…or…to hold a substrate
Two or more chains bind to give a….and form a….structure
Fold into compact, globular shape
Tertiary structure
Pocket or active site
Functional molecule, quaternary structure
The 5 interactions/ bonding that is holding the tertiary and quaternary proteins together are…
- H bonds= (between H atoms) covalently bound to proton donor and acceptor
- Ionic= charged amino acids, often surface exposed on outside
- Disulfide= between cysteine residues
- Van der waals= weak electrostatic forces of attraction
- Hydrophobic interactions= between hydrophobic residues often on the inside of proteins
5 types of protein functions:
- Structural= cytoskeletal
- Regulatory= chaperones
- Carriers= membrane transporters
- Catalytic= enzymes
- Sensory= receptors
Protein misfolding results in….and it can be driven by…
Disease
Change in primary sequence or escape from negative folding pathway
Prion diseases are….
Can originate through…or…
Caused by accumulation of…
Fatal neurodegenerative diseases
Transmission or inheritance
Prion protein aggregates
Misfolding of amyloid protein results in…with…
Formation of fibrils
Cross-beta structure that cannot be degraded
Amyloid beta are associated with….
Alzheimer’s disease
Hb vs Mb
Hb= allosteric, co-operative, affinity changes by pH and CO2, regulated by biphosphateglycerate
Mb= non co-op, not affected by pH, CO2 or BPG
The 2 states of Hb
R state= relaxed= less salt bridges between units= high affinity of O2
T state= tense= more salt bridges= low affinity of O2 (de-oxy state since no O2 is bound)
Hb in lungs vs tissue
Loading and unloading
Lungs= lots of O2= high affinity so more O2 bind to Hb
Tissue= less O2= low affinity so more O2 released
When one O2 release= protein changes shape promoting the 3 other to quickly release/ when one O2 binds (hardest to bind)= protein changes shape so its easier for the rest to bind
Bohr effect= Hb has less affinity for O2 when:
PH is lower/ more H+/ due to increased CO2 or lactic acid in blood (to promote fast release of O2 to tissue and muscle quickly)
Why do H+affect O2 binding
PH affects protonation state of amino acid residues (particularly histidine)= H+ conc is high= residues protonated= more positively charged
Form new salt bridges= stabilise T state (more tense due to increases salt bridges= decrease affinity for O2)
2,3- BPG is…and is found at high conc in…
The structure of BPG is..charged
It…affinity of O2
BPG levels are…at high altitude and under…conditions
This means Hb releases…O2 in these 2 situations
2,3- Biphosphateglycerate
RBC
Negatively (phosphate groups are negative)
Decreases
Increased, hypoxic (lack of O2 in tissue)
More
BPG binds in the space between…so HbF…
Negative charges of BPG interact with..
Beta chains
Is not affected by BPG
Positive amino acid residues
H+, CO2 and BPG interact at….sites
So their effects can be…
Different
Additive
HbF has…than HbA
It pro-dominates during last 2….and by end of fist year our body makes entirely…
Higher affinity to O2
Trimesters of gestation
HbA
HbA vs HbF
- Both have 4 subunits
- 2 identical alpha subunits
- HbF= 2 gamma subunits (instead of beta)
- Gamma increases affinity for O2
5.no beta chains= no 2,3-BPG binding - BPG reduces affinity in HbA= so under same conditions, HbA will release O2 and HbF will capture it
How do mutations affect haemoglobin:
- Amount of Hb synthesised
- Structure (ie subunit interfaces)
- Stability of Hb= leading to haemolytic anaemia
- Affinity for O2
- Affinity for regulators (ie BPG)
Types of position mutations in Hb:
Position (mutations in critical residues will affect function ie: promoter region/ exon splice site/ protein structure)
Types: 1. Conservative= maintains properties (non-polar replaced with non-polar residue)
2. Non-conservative= changes properties
2 haemoglobinopathies (opathies= disease suffix)
- Sickly cell anaemia (affects Hb structure)
- Beta-thalassaemia (affects Hb production)
Sickly cell heamoglobin=…
Is caused by…
HbS
Mutation in beta-globin chain (beta chain subunit)= (B6 Glu is replaced by Val)
HbS makes…patches in subunit surface and it…
They stick together to form…that distort shape of RBC= sickle
Sticky hydrophobic
Sticks to another hydrophobic patch
Long fibres
Sickly cell crisis occurs when…
It lasts for…
Other symptoms are…
Its treated by…
Sicked RBC becomes trapped within small blood vessels and block them= damage organs
7 days
Tiredness, headaches, dizziness, increased infection risks
Fluids, painkiller, antibiotics, transfusions (no cure)
Sickle cell anaemia is an…
Sickle cell trait=…
It occurs more in geographical areas with…as it gives a…against malaria
Autosomal recessive disease
Carrier= one copy of mutated beta globin
High incidence of malaria
Protective effect
HbF can be a…to sickle cell because it…
As…% of HbF in blood reduces the symptoms
…therapy is researched to increase level of HbF
…anticancer drug that is shown to be effective as it increased HbF levels
Solution
Lacks beta chains
20
Gene therapy (surpresses a silencer of HbF gene= more is expressed)
Hydroxyurea
Thalassaemia effects…and its caused by…
The severity depends on…
Less Hb=…
Production of haemoglobin
Reduction or absence of alpha or beta chains
Type
Less HbS= less sickling
