A nucleic acid consists of four kinds of bases linked to a sugar-phosphate backbone.

A monomer unit

The double-helical structure of DNA facilitates the replication of the genetic material

(10 nucleotides)

The double helix can be reversibly melted

Single –stranded DNA absorbs light more effectively than does double-helical DNA-----Hypochromism.

The absorbance of a DNA solution at 260nm increased when the double helix is melted into single strands.

● In eukaryotes, the processes of transcription and translation are separated both spatially and in time. Transcription of DNA into mRNA occurs in the nucleus. Translation of mRNA into polypeptides occurs on ribosomes.

Lipids and Cell Membrane

Structure of biomembraneHead group

Fatty acid

Electron micrograph of red blood cell plasma membrane

Electron micrograph of red blood cell plasma membrane

Confocal image of ERD-GFP (an ER marker)

Common feagures of biological membrane

1. Membranes are sheet-like structures, only two molecules thick, that form closed boundaries between different compartments. The thickness of most membranes is between 6 nm and 10 nm.

2. Membrane consist mainly of lipids and proteins. Their mass ratio ranges from 1:4 to 4:1. Membranes also contain carbohydrates that are linked to lipids and proteins.

3. Membrane lipids have both hydrophilic and hydrophobic moieties. These lipid bilayers are barriers to the flow of polar molecules.

4. Specific proteins mediate distinctive functions of membrane.

5. Membranes are noncovalent assemblies. The constituent proteins and lipid molecules are held together by many noncovalent interactions.

6. Membranes are asymmetric. The two faces of biological membranes always differ from each other.

7. Membranes are fluid structures. Lipid and protein molecules diffuse rapidly, unless they are anchored by specific interactions. Membranes can be regarded as two-dementional solutions of oriented proteins and lipids.

8. Most cell membranes are electrically polarized. Membrane potential plays a key role in transport, energy conversion, and excitability.

Common feagures of biological membrane

Fatty Acids are key conponents of lipids

Structure of biomembraneHead group

Fatty acid

General Features of Fatty Acid Structure

The elements of fatty acid structure are quite simple. There are two essential features:

1. A long hydrocarbon chain ●The chain length ranges from 4 to 30 carbons; 12-24 is

most common. ● The chain is typically linear, and usually contains an even

number of carbons.

2. A carboxylic acid group

The many fatty acids which occur naturally arise primarily through variation of chain length and degree of saturation.

Carbon-Carbon Double Bonds

Carbon-carbon double bonds (unsaturations) are found in naturally occurring fatty acids. There may be one double bond or many, up to six in important fatty acids. Fatty acids with one double bond are the most prevalent in the human body, comprising about half of the total. Fatty acids with two or more double bonds occur in lesser quantities, but are extremely important.

When double bonds occur they are almost always cis. If there is more than double bond, they occur at three-carbon intervals, e.g., -C=C-C-C=C-. This is called the divinylmethane pattern.

Classification of Fatty Acids

One system of fatty acid classification is based on the number of double bonds.

● 0 double bonds: saturated fatty acids

● 1 double bond: monounsaturated fatty acids

● 2 or more double bonds: polyunsaturated fatty acids

Phospholipids are the major class of membrane lipids

Hydrophobic hydrophilic

Amphipathic

Cholesterol is a lipid based on a steriod Nucleus

Cholesterol is a lipid based on a steriod Nucleus

4 linked hydrocarbon rings

Cholesterol is a lipid based on a steriod Nucleus

Interact with phospholipid head group

A micelle

Membrane formation is a consequence of the amphipathic nature of the lipids

A section of a bilayer membrane

leaflets

The favored structure for most phospholipids and glycolipids in aqueous media is a bimolecular sheet rather than a micelle.

Hydrophobic interactions have three significant biological consequences:

1. Lipid bilayers have an inherent tendency to be extensive.

2. Lipid bilayers tends to close on themselves so that there are no edges with exposed hydrocarbon chains, and so they form compartments.

3. Lipid bilayer are self-sealing because a hole in a bilayer is energetically unfavorable.

• Lipid bilayer are highly impeameable to ions and most polar molecules.

• Water is a conspicuous exception. It traverses such membrane because of its small size, high concentration, and lack of a complete charge.

Proteins carry out most membrane processes

SDS-acrylamide gel patterns of membrane proteins

Immunofluorescent staining of a plasmamembrane protein

Proteins associate with the lipid bilayer in a variety of ways

Integral membrane protein: a, b, c.

Peripheral membrane protein: d, e.

Proteins interact with membranes in a variety of ways

Protein can span the membrane with alpha helices which are the most common structural motif in membrane proteins.

A channel protein can be formed from Beta strands

hydrophilic

hydrophobic

40分钟由以上实验中蛋白质的分布变化，你能得出什么结论？

细胞膜具有一定的流动性

•一个典型的科学实验 ( 用不同颜色的荧光标记不同细胞膜上的蛋白质 )

Lipids and many membrane proteins diffuse rapidly in the plane of the membrane

FRAP: Fluorescence recovery after photobleaching

The fluid mosaic model allows lateral movement but not rotation through the membrane

Membrane fluidity is controlled by fatty acid composition and cholesterol content

● All biological Membranes asymmetric.

● The outer and inner surface of all known biological membranes have different components and different enzymatic activities.

Proteins are targeted to specific compartments by signal sequences

Proteins are targeted to specific compartments by signal sequences

Proteins are targeted to specific compartments by signal sequences

Phase separation in model membranes

Micron-scale fluid/fluid phase separation in giant unilamellar vesicles (GUVS) composed of cholesterol, SM, DOPC, and ganglioside GM1. Tangential confocal section of GUV imaged at 23 °C. Alexa488-cholera toxin B (A488-CTB) bound to Lo-preferring GM1 partitions complementarily to the Ld-preferring carbocyanine lipid probe C12:0 DiI in phase-separated GUVs (scale bar, 5 μm).

Lipid rafts and domains in the plasma membrane

Giant plasma membrane vesicles (GPMVs) isolated from RBL-2H3 mast cells spontaneously phase separate into coexisting fluid phases. GPMVs were generated from cells pre-labeled with Alexa488-cholera toxin B and lissamine rhodamine B sulfonyl-DOPE (Rh-DOPE). Equatorial confocal section of a GPMV ( 25 μm diameter) was imaged at 15C. A488-CTB bound to GM

1 shows partitioning complementary to Rh-DOPE and prefers the Lo phase in GPMVs.

Summary

○ Many common features underlie the diversity of biological membrane

○ Fatty acid are key constituents of lipid

○ There are three common types of membrane lipids: phosphlipids, glycolipids and cholesterol.

○ Protein associate with the lipid bilayer in a variety of way.

○ Lipids and many membrane proteins diffuse rapidly in the plane of the membrane

Selected readings

De Weer, P. 2000. a century of thinking about cell membranes. Annu. Rev. Physiol. 62: 919-926

White SH and wimley WC. 1999. Membrane protein folding and stability: Physical principles. Annu. Rev. Biophys. Biomol. Struct. 28: 319-365.

Gunnar von Heijne. 2006. Membrane-protein topology. Nature Reviews Molecular Cell Biology 7, 909 – 918

John F. Hancock. 2006. Lipid rafts: contentious only from simplistic standpoints. Nature Reviews Molecular Cell Biology 7, 456-462