1.3 - Membrane Proteins Flashcards
Protein structure relates to function
- Proteins undergo conformational changes to alter their function
- Conformation changes require specific biological signal
- Stable bioelectric environments are required for protein and membrane function (more details sep card)
- Proteins must be hydrated (more details sep card)
- Eg haemoglobin, VG sodium channels, ATPases, GPCRs, phosphokinases etc
Stable bioelectric environment required for protein + membrane function
- Require special electric environment
- Requires concentration of specific ions eg Na+, K+, Cl- and Ca 2+
- Outside cell, net positive charge
- Inside cell, net negative charge
- This generates an electric field
Functioning proteins need to be optimally hydrated to attain their 3D structure
- Proteins need to incorporate water as an essential part of their biological structure
- Very dynamic → like a cloud of water moving around the structure forming Hδ+ and Oδ- bonding
- Water stays away from hydrophobic regions of proteins, and this contributes to the shaping of proteins
Membrane protein mobility
- Proteins can flex and do ‘wobbly bob’ (but much more slowly than lipids)
- Random mobility is limited as proteins have much larger and more complex 3D structure
- lateral movement permitted – formation of protein complexes
- rotational movement permitted
- conformational change permitted, which is vital for function. This is not random
- Proteins cannot flip-flop as they are too large and require too much energy to do this spontaneously
How are membrane proteins classified
peripheral aka extrinsic
- Bound to the surface of the membrane via electrostatic and hydrogen bond interactions with the polar head groups of phospholipids
- Can become dissociated from the membrane (unlike integral) by disturbances in pH (as this will change the ionic configuration of AA residues)
- Eg G-proteins, cytoskeletal proteins, electron carriers (eg cytochrome C) and some enzymes
- Can either be:
☞ intracellular where they are associated with the internal membrane face
☞ extracellular where they are associated with the external membrane face
integral aka intrinsic
- these are embedded within the phospholipid bilayer
- may or may not span the entire width of the membrane (transmembrane)
- cannot be removed by pH ionic change
- extensive hydrophobic domain in order to interact with the hydrocarbon tails of the lipid bilayer
- eg channels, transporters, receptors, adhesion proteins + some enzymes
Intracellular peripheral proteins
- Associated with internal membrane face
- Wide range of functions (eg enzymes, regulatory proteins for channels/transporters)
- Central roles in cytoskeletal megastructure provides flexibility + elasticity of whole cell membrane
- Disperses forces throughout network, protecting cell integrity from mechanical disruption
Extracellular peripheral proteins
- Associated with external membrane face
- Wide range of functions (eg enzymes, antigens, adhesive molecules with extracellular matrix)
- Adhesive molecules: essential for transmission of mechanical force generated by individual cells
Integral membrane proteins
- Varying degrees of penetration of the lipid bilayer
- Not removed by pH ionic change
- Associated with membrane topology (ie how membrane retains shape)
- Extensive non-polar bonding occurs within the hydrophobic interior of the lipid bilayer
- AA residuals within the bilayer are non-polar
- Peptide chains on external + internal membrane face have mainly polar residuals
- Interact with local lipid polar head groups / peripheral proteins / water / ions
What are lipid anchored proteins
- Often included in ‘integral proteins’ category
- This due to covalent link via fatty acid/lipid group within bilayer
- Functional protein is outside membrane, and can move laterally
- Eg lipid anchored G-proteins are activated by a receptor molecule extracellularly
Higher levels of membrane-protein organisation
- Some individual membrane proteins move through membrane laterally in order to perform function
- Other membrane functions do not function in isolation → form part of a group/complex
- Different levels of scale of membrane-protein interaction:
☞ aggregation where many proteins act as a larger aggregate to perform particular function (eg respiratory chain complex)
☞ tethering - this can be extracellular or intracellular. Eg in intracellular tethering, the RBC membrane proteins connect with the cytoskeleton in order to provide structural strength, while allowing whole cell flexibility and elasticity. Distributes forces within cell / over cell membrane
☞ cell-cell interactions connecting cells to other cells (eg cadherin proteins) to form tissues. Also can perform mechano and chemo sensory signalling role and transmitting forces throughout the tissue
Overview of RBC cortical cytoskeleton
- RBC needs to keep its shape (bioconcave for SA)
- But also needs flexibility in order to be able to fit into small capillaries
- RBC have a cytoskeleton
- Achieved by vertical interaction between the membrane, its associated membrane proteins and the cytoskeleton
three main structural components
1. Transmembrane proteins
2. Intermediate anchoring proteins (connecting 1 + 3)
3. Long flexible / elastic force carrying proteins
What are the proteins involved in the erythrocyte cell membrane (details of roles in separate cards)
transmembrane proteins
Band 3.1 and glycophorin
intermediate anchoring proteins
Ankyrin
Adducin-actin-band 4.1
force carrying proteins (forming the ‘mesh’ of cytoskeleton)
Spectrin
What are the functions of band 3.1 (and glycophorin)
**band 3.1 **
- A Cl-/HCO3- exchanger
- Integral protein
- Essential transporter in carriage of CO2
glycophorin
- Antigen
- Reduces adhesive/friction forces
both
- Shape bioconcave architecture
- Enabling range of forces to be acting on membrane/cell to be distributed throughout the whole RBC structure
What are the functions of ankyrin and band 4.1
ankyrin
Anchors band 3.1 to spectrin
band 4.1
- Anchors glycophorin to spectrin
- Also acts with adducin that stabilises the assembly
- Also acts with F-actin that forms short rods to stabilise further
- These all interact via polar bonds
Features + function of spectrin
- Forms flexible and elastic double helical structure
- Made up of two multi-unit chains α and β that are joined at end
- At the end of chains it forms heterotetramers with other spectrins using the band 4.1-adducin-actin
- Repeating structure: forms a hexagonal ‘mesh’
- Spectrin matrix throughout the whole RBC
- This transmits forces throughout the whole RBC
