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Biological Membranes and Transport

Lehninger 3rd ed. Chapter 12

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Biological membranes •  Membranes form the external boundaries of cells. •  As such they represent the communication posts

of the cell with the world. •  In eukaryotic organisms they also define several

different internal compartments. •  Membranes are selectively permeable to a large

number of chemicals. •  About 30% of the proteins in our genome reside in

the membrane.

3 Cilium Mitochondrion

Endoplasmic reticulum Secretory vesicle

Cell body

Digestive vacuole

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Membrane composition •  Lipids (see previous lecture). •  Proteins. •  Carbohydrates.

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• Each type of membrane has a characteristic composition of lipids and proteins. • The composition may reflect the metabolic rate of that membrane.

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The architecture of membranes

•  Of all of the three components that make up a membrane, only lipids on their can form membranes.

•  Since lipids are amphipathic, they form aggregates placing their polar groups close to one another and their apolar groups to one another.

•  The resulting shape of the aggregate depends on the structure of the lipid.

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•  Different lipids with different shapes are more suited to different leaflets of the bilayer.

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The lipid bilayer is a 2 dimensional fluid

Heat

Flip flop

Lateral diffusion

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Membrane composition influences fluidity •  Shorter chains increases fluidity. •  Double bonds increase fluidity. •  Sterols decrease fluidity. •  Organisms regulate their lipid composition to

ensure fluidity of their bilayer.

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13 Membrane proteins diffuse in the bilayer as well (but slower) unless they are prevented.

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What are membrane proteins? •  There is a simple operative definition for a membrane

protein: When you centrifuge down membranes, does your protein precipitate? If it does than it a membrane protein.

•  If you need only salt to make it soluble, then the protein is a peripheral membrane protein.

•  If you need to add an agent that destroys the bilayer (e.g. detergent or an organic solvent) in order to solubilize the protein, then you can safely state that your protein is an integral membrane protein.

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•  Integral membrane proteins

•  can be of two varieties: 1.  A lipid moiety

covalently bound to the protein: (e.g. isoprene, fatty acid PI).

2.  The protein its self traverses the lipid bilayer.

•  Very few proteins can be both water and membrane soluble.

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Integral membrane proteins •  Integral membrane proteins reside in the lipid

bilayer that is very hydrophobic and, has no groups capable of H-bonding.

•  Therefore the protein must: – Self-satisfy its H-bonding potential. – Contain hydrophobic amino acids to face the

lipid bilayer. •  The 2 most common ways that this is achieved, is

by forming α-helical bundles and β-barrels.

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α-helical membrane proteins

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Bacteriorhodopsin: a light driven H+ pump.

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Photosynthetic reaction center: the source of life on earth!

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Topology prediction of membrane proteins

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β-barrel ���(a.k.a porins)

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Integral membrane proteins are highly abundant and highly important

•  Highly abundant: 20-30% of our genomes code for membrane proteins.

•  Highly important for biomedicine: >80% of all drugs target membrane proteins.

•  Dramatically underrepresented in the protein structural data base due to experimental difficulties in determining their structures.

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Membrane fusion and fission •  Membrane fusion is the process in which two opposing

membranes are joined into one contiguous membrane. •  The proteins that reside in the membrane retain their

relative orientations in biological fusion. In “synthetic” fusion events proteins tend to get “randomized”.

•  There is no leakage of ions or any other small compounds in biological fusion.

•  Fission is simply the reverse of fusion. •  Both fusion and fission are exceptionally common events

in biology.

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Solute transport across membranes

•  The permeability of the membrane is modified by the presence of a huge number of unique proteins that can be divided into 3 general classes. – Channels. – Facilitators. – Pump.

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Channels •  Mostly selective holes that allow very small

molecules (e.g. ions and water) to traverse the lipid bilayer according to their electro-chemical potentials.

•  The flux can be of the order of 107 molecules per second.

•  How can such a flux be maintained alongside specificity?

•  Ion fluxes are the way in which electrical signal are transmitted in the body.

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Facilitators

•  Proteins that allow relatively larger molecules (e.g. sugars, amino acids bicarbonate) to traverse the lipid bilayer according to their electrochemical gradient are called Facilitators, or transporters.

•  Some work by allowing more than 1 molecule to traverse the bilayer at once.

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Active transport via pumps

•  In some instances proteins can “move” a molecule across the membrane against its electro-chemical gradient.

•  For example [Ca2+] in the cytoplasm is ~0.1µM but in the ER lumen and in the extra-cellular media is ~1mM.

•  Thus, there must be an active transport of across the membrane.

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Primary transport

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Active co-transporters

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