lecture 18 - lipid bilayers and membrane proteins

8/16/2019 Lecture 18 - Lipid Bilayers and Membrane Proteins

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General BiochemistryChem560 Spring 2016

Lecture 18

Lipid Bilayers and Membrane Proteins

Manal A. Swairjo, Ph.D.

4/7/2016


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Chapter 9Lipid Bilayers

Learning Objectives• Why do glycerophospholipids and sphingolipids—but not fatty acids—f

• Explain why lateral diffusion of membrane lipids is faster than transvers

• What factors influence the fluidity of a bilayer?

• Explain the differences between integral and peripheral membrane pro

• What are the two types of secondary structures that occur in transmemproteins?

• Describe the covalent modifications of lipid-linked proteins. Why might

these modifications be reversible?


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Aggregates of Single-Tailed Lipids

These two are unfavorable due to water-filled ce

Too many lipid monomers per micelle.Ideal spheroidal micelle

From few hundred molecules

Wedge shaped


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Phospholipids (double tailed) form

favorable disk micelles with bilayer

Rectangular shape


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Phospholipids in aqueous solution

spontaneously form liposomes

• Liposome: spheroid shaped solvent filled

vesicle bound by a single phospholipid

bilayer.

• Very stable structures.

• Several hundred Angstroms in diameter.

• Used for drug delivery because they

readily fuse with cell membranes.


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Diffusion in Phospholipid Bilayer

• Rare event. Half time of several days.• Reason: polar headgroups have to cross the hydrophobic core.

• Occurs all the time. Very fast speed of 1 micron per second.

• Therefore, phospholipid bilayers are considered a 2D fluid.

• Note this is just a schematic showing the acyl chains as stiff.

In fact they are not.


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A more realistic view of the fluid bilayer

• This is a computer generated model.

• Molecular dynamics simulation calculations

show that the core is more fluid than the polar

surface.

• The acyl chains are in constant motion due to

rotations around the C-C bonds.

• Note that the acyl chains interdigitate to form atight seal.

• Note that water penetrates only in between the

polar head group.

• Head groups bob up and down.

• Unsaturated acyl chains (with double bonds) kink

and fill the gaps.

15 Å

30 Å

15 Å


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Phase Transition in Lipid BilayersNote: why does cholesterol decrease membrane fluidi

• The whole lipid molecule is highly mobile.

• The nonpolar tail is “wiggling” and bending,

hence thin bilayer.

• “Liquid crystal” state.

• Nonpolar tails are straight

thick bilayer.

• They form more orderly a

• Gel like solid.


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Integral (Intrinsic) Membrane Proteins are T

Membrane Associated

Crystal structurAquaporin

• Phospholipid molecules bound to the

protein.

• Acyl chains conform to the protein

hydrophobic surface.

• The protein thickness matches themembrane thickness.

• Membrane proteins can be extracted from

membranes with detergents (e.g. SDS) and

purified by gel filtration but require

detergent to stay soluble.


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Integral Proteins are Asymmetrically Oriented Amphiphi

i.e. they are found oriented in one direction relative to the me

Example of a transmembrane protein: human gylco

Human glycophorin A in

membranes of red blood cells.

Heavily glycosylated and this makes

cell membrane hydrophilic so RBCs

flow easily in blood plasma and donot stick.


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All transmembrane (TM) segments of memb

proteins consist of either alpha helices or

sheets.

Seven α Helices: Bacteriorhodopsin

(7-TM protein).

Beta barrel: Which face of the

TM segments can be predicted from the

amphiphlicity profiles of the sequence.

Amphipathic helices: their hydrophobicsides face the membrane core.


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OmpF porin is a β Barrel Trimer and i

Hydrophobic Band Immersed in Membr


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Lipid Modifications Anchor Proteins to

• Isoprenoids (C15 and C20 shown). They get

enzymatically linked to proteins at a C-terminal

Cys.

• Myristoylation: C14 fatty acid attached to N-term

Gly.

• Palmitoylation: C16 fatty acid attached to specific

Cys.


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Peripheral membrane proteins are on the surface of the

and dissociate easily They are double faced Example: A

bind to bilayer in a calcium dependent manner

Chapter 9


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Chapter 9Lipid Bilayers and Membrane Proteins

Key Concepts

Certain amphiphilic molecules form bilayers.

• The bilayer is a fluid structure in which lipids rapidly diffuse

laterally.

• Integral membrane proteins contain a transmembrane

structure consisting of α helices or a β barrel with a

hydrophobic surface.• Lipid-linked proteins have a covalently attached prenyl

group, fatty acyl group, or glycosylphosphatidylinositol

group.

• Peripheral membrane proteins interact noncovalently with

proteins or lipids at the membrane surface.

lecture 18 - lipid bilayers and membrane proteins

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