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III. Membrane Composition

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B. Proteins The membrane’s lipid core seals the cell in an envelope across which only lipid-soluble materials, such as O 2 , CO 2 , and alcohol can cross. Cells exist in an aqueous world, however, and most of the molecules that they need to thrive are hydrophilic and cannot penetrate the lipid core. Thus, the surface ( plasma ) membrane also contains proteins whose function is to help ions and other charged molecules across the lipid barrier. Membrane proteins also allow for intercellular com- munication and provide cells with sensory information about the ex- ternal environment. Proteins are grouped on the basis whether they localize to the membrane surface ( peripheral ) or are integral to the lipid bilayer (Figure 1.5). 1. Peripheral: Peripheral proteins are found on the membrane sur- face. Their link to the membrane is relatively weak and, thus, they can easily be washed free using simple salt solutions. Peripheral proteins associate with both the intracellular and extracellular plasma membrane surfaces. a. Intracellular: Proteins that localize to the intracellular surface include many enzymes; regulatory subunits of ion channels, receptors, and transporters; and proteins involved in vesicle trafficking and membrane fusion as well as proteins that tether the membrane to a dense network of fibrils lying just beneath its inner surface. The network is composed of spectrin, actin, ankrin, and several other molecules that link together to form a subcortical cytoskeleton (see Figure 1.5). b. Extracellular: Proteins located on the extracellular surface include enzymes, antigens, and adhesion molecules. Many peripheral proteins are attached to the membrane via gly- cophosphatidylinositol ([ GPI ] a glycosylated phospholipid) and are known collectively as GPI-anchored proteins . 2. Integral: Integral membrane proteins penetrate the lipid core. They are anchored by covalent bonds to surrounding structures

Cholesterol

Phospholipid

Polar head group

Hydrophobic tail

Figure 1.4 Cholesterol location with the membrane.

Integral membrane proteins

Extracellular fluid

Peripheral membrane proteins

Cytoskeleton

Intracellular fluid

Figure 1.5 Membrane proteins.

Clinical Application 1.1: Paroxysmal Nocturnal Hemoglobinuria

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, inherited disease caused by a defect in the gene that encodes phosphati- dylinositol glycan A. This protein is required for synthesis of the glycophosphatidylinositol anchor used to tether peripheral proteins to the outside of the cell membrane. The gene defect prevents cells from expressing proteins that normally protect them from the immune system. The nighttime appearance of hemoglobin in urine (hemoglobinuria) reflects red blood cell lysis by immune comple- ment. Patients typically manifest symptoms associated with ane- mia. PNH is associated with a significant risk of morbidity, in part, because patients are prone to thrombotic events. The reason for the increased incidence of thrombosis is not well delineated.

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