Chapter 10 Membrane Structure

All biological membranes have a common structure – each is a very thin film of lipid and protein molecules held together by noncovalent interactions

Membrane lipids are amphipathic molecules, most of which The Lipid Bilayer Membrane lipids are amphipathic molecules, most of which spontaneously form bilayers

The most abundant membrane lipids are the phospholipids Phospholipids have a polar head group and two hydrophobic hydrocarbon tails

The tails are usually fatty acids, and they can differ in length. One tail usually has one or more cis-double bonds, while the other does not.

The shape and amphipathic nature of the lipid molecules cause them to form bilayers spontaneouly in aqueous environments.

Hydrophilic and hydrophobic molecules interact differently with water

molecules spontaneously form bilayers in aqueous environments Packing arrangements of lipid molecules in an aqueous environment Lipid molecules spontaneously aggregate to bury their hydrophobic tails in the interior and expose their hydrophilic heads to water. Being cylindrical, phospholipid molecules spontaneously form bilayers in aqueous environments

the phospholipid molecule The spontaneous closure of a phospholipid bilayer to form a sealed compartment The formation of a sealed compartment is fundamental to the creation of a living cell, and this behavior follows directly from the shape and amphipathic nature of the phospholipid molecule

The lipid bilayer is a two-dimensional fluid Individual lipid molecules are able to diffuse freely within lipid bilayers. Demonstrated using synthetic lipid bilayers and electron spin resonance (ESR) spectroscopy Liposomes

A black membrane

Phospholipid mobility

The fluidity of a lipid bilayer depends on its composition and its temperature The membrane becomes more difficult to freeze if the hydrocarbon chains are short or have double bonds, so that the membrane remains fluid at lower temperatures

phospholipids, it often also contains cholesterol and glycolipids The lipid bilayer of many cell membranes is not composed exclusively of phospholipids, it often also contains cholesterol and glycolipids

Eucaryotic plasma membranes contain large amounts of cholesterol

Four major phospholipids predominate in the plasma membrane of mammalian cells

Lipid bilayers can form domains of different compositions Lipid phase separation in artificial lipid bilayers (A) 1:1 mixture of phosphatidylcholine and sphingomyelin (B) 1:1:1 mixture of phosphatidylcholine, sphingomyelin, and cholesterol

cholesterol, and some membrane proteins Plasma membrane contains lipid rafts that are enriched in sphingolipids, cholesterol, and some membrane proteins Lipid rafts are small specialized areas in membranes where some lipids (primarily sphingolipids and cholesterol) and proteins are concentrated

Lipid droplets are surrounded by a phospholipid monolayer

The asymmetry of the lipid bilayer is functionally important The lipid bilayer of human red blood cells

Signaling functions of inositol phospholipids in the cytosolic leaflet of the plasma membrane

Glycolipids are found on the surface of all plasma membranes

Membrane Proteins

Membrane proteins can be associated with the lipid bilayer in various ways

Covalent attachment of a protein to the membrane by a fatty acid chain or a prenyl group

in an α-helical conformation In most transmembrane proteins the polypeptide chain crosses the lipid bilayer in an α-helical conformation

Membrane regions and preferred amino-acid locations Membrane regions and preferred amino-acid locations. A snapshot of a lipid bilayer membrane and its three major regions. Grey, carbon atoms; red, oxygen; white, hydrogen bound to oxygen; orange, phosphorus. In an a-helix, 20 amino acids (blue) can span the hydrocarbon core, and 10 amino acids (green) can span the interfacial region. Arrows indicate where most of each amino acid (denoted by its three-letter symbol) would be found at equilibrium based on transfer free-energy measurements (Nature, 2005, Vol 433, 367-369)

A possible scheme for the membrane-insertion decision, as proposed by Hessa et al. A top view of the membrane and the translocon pore that crosses it. Inside the pore is a peptide helix surrounded by water. The pore opens sideways into the membrane, allowing the helix to interact with the membrane lipids. If the peptide is more compatible with lipid than with water, it will transfer into the membrane; otherwise, it will continue to be moved through the pore. The figure is only intended to convey the basic principle, and omits many mechanistic and structural issues. (Nature, 2005, Vol 433, 367-369)

Hydropathy plots identify potential α-helical segments in a polypeptide chain

Two a helices in the aquaporin water channel, each of which spans only halfway through the lipid bilayer

Converting a single-chain multipass protein into a two-chain multipass protein

Steps in the folding of a multipass transmembrane protein

hydrogen-binding requirements is for multiple transmembrane strands An alternative way for peptide bonds in the lipid bilayer to satisfy their hydrogen-binding requirements is for multiple transmembrane strands of polypeptide chains to be arranged as β sheet in the form of a closed barrel

Many membrane proteins are glycosylated and have intrachain or interchain disulfide bonds

The cell coat, or glycocalyx is the carbohydrate-rich zone on the cell surface Likely functions – protect cells against mechanical and chemical damage keep foreign objects and other cells at a distance

A simplified diagram of the cell coat (glycocalyx)

Membrane proteins can be solubilized and purified in detergents

Structure and function of detergent micelles

Solubilizing membrane proteins with a mild detergent

functional membrane systems The use of mild detergents for solubilizing, purifying, and reconstituting functional membrane systems

that contain bacteriorhodopsin molecules Bacteriorhodopsin is a proton pump that traverses the lipid bilayer as seven α helices The archaean Halobacterium salinarum showing patches of purple membrane that contain bacteriorhodopsin molecules

The three-dimensional structure of a bacteriorhodopsin molecule

Rhodopseudomonas viridis Membrane proteins often function as large complexes The three-dimensional structure of the photosynthetic reaction center of the bacterium Rhodopseudomonas viridis

Many membrane proteins diffuse in the plane of the membrane

Fluorescence recovery after photobleaching

Fluorescence loss in photobleaching

Plasma membrane proteins are restricted to particular membrane domains

Three domains in the plasma membrane of a sperm cell

Four ways of restricting the lateral mobility of specific plasma membrane proteins

The cytosolic side of plasma membrane proteins can be studied in red blood cell ghosts

The spectrin-based cytoskeleton on the cytosolic side of the human RBC membrane