III. Membrane Composition
3
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
Figure 1.4
Cholesterol location with the membrane.
Polar head
group
Hydrophobic
tail
Phospholipid
Cholesterol
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.
Integral membrane
proteins
Intracellular
fluid
Extracellular
fluid
Peripheral
membrane
proteins
Cytoskeleton
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