principles of membrane proteins structure. summary of biological membranes highly selective...
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Principles of Membrane proteins Structure
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Summary of Biological Membranes
• Highly selective permeability barriers• Amphiphilic organization• Fluid Mosaic model: liquid and
asymmetric• Fluidity and thickness of membranes are
determined by their lipid composition (saturated, longer chains make it less fluid)
• Hydrophobic core • Hydrophilic Surfaces
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• Integral - membrane spanningMain interaction is vdW interaction with the
hydrophobic core of the bilayer; therefore, can be isolated from membrane only through membrane disruption, e.g., by detergents; GPCRs, rhodopsins, channels, …
• Peripheral –Do not penetrate the hydrophobic core; main
interaction is electrostatic interaction with one of the hydrophilic surfaces of the bilayer; usually associated with integral membrane proteins; can be isolated from membrane by strong salt or by changing pH; Cytochrome C
Membrane Proteins
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•The bilayer fabric of the membrane has two chemically distinct regions:
Hydrophobic coreInterfaces
Hydrocarbon
Water
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• Polar/Hydrophilic groups:Backbone (C=O and N-
H)Polar side chains (polar
or charged)
• Hydrophobic groups:Hydrophobic side chains
(R)
Major interactions in a protein
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A few calculated numbers
water
alkane
2.1 kcal/mole
6.4 kcal/mole
~4.0kcal/mole
Unfolding of a helix in membrane has an energetic cost of about 4.0 kcal/mole/peptide bond. Unfolded proteins cannot exist in membrane.A transmembrane helix of 25 residues forms ~20 hydrogen bonds between its backbone groups.
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Common Folds of Membrane Proteins
Hydrogen-bond forming groups are satisfied.
-helix-sheet
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-helical – the most common structural fold in membrane proteins: rhodopsins, GPCRs, F0-ATPase, MscL, aquaporins, ion channels, …
-barrel – Porins: OmpF
Common Folds of Membrane Proteins
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-helical Membrane Proteins
Rhodopsin Bacteriorhodopsin
Check GlpF in VMD
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-helical Membrane Proteins
Bacterial Photosynthetic Membrane
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-barrel Membrane Proteins
~18 -strands – found in outer membranes of G- bacteria and mitocondriaDiameter = minimum 7.0 Å
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-barrel Membrane Proteins
Check OmpF in VMD
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• Non-polar residues interact with the hydrophobic core of the membrane
• Polar residues interact with head groups and aqueous solution.
Role of side chains
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MaltoporinOmpF GlpF AQP1
Protein-Membrane Interaction
Prediction of transmembrane regions?
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Cysteine(Cys, C)
Proline(Pro, P)
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Hydropathy Plots
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Failures:• False positive: hydrophobic parts of globular
proteins• beta-barrel structures • helices including a highly hydrophilic surface • Assembly of transmembrane helices cannot be
predicted
Prediction of transmembrane regions of membrane proteins by hydropathy plots …
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Aromatic side chains, in particular tyrosines, are found at the interface of hydrophobic and hydrophilic layers of the bilayer
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Membrane-anchored proteins
Prostaglandin H2-synthase needs to be close to membrane, since its substrate, arachidonic acid, is a fatty acid in the membrane and cannot be found in cytoplasm.
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Reverse bundles: Hydrophobic inside, hydrophilic outside
Prostaglandin H2-synthase
Site of action of ASPIRIN
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Covalent Tethering of Membrane Proteins to Membranes
outside
Critical for protein function: L O C A T I O N
Often found in proteins involved in cell signaling