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C. HO W MANY MEMBRANE PROTEIN TYPES ARE T HERE?
This is a very difficult question to answer with any certainty as it is subject to interpreta-
tion. One membrane type gradually blends into another. A first crude approximation could
classify proteins as either peripheral (extrinsic) or integral (intrinsic). Peripheral proteins are
essentially water-soluble globular proteins that are attached to the membrane surface
through electrostatic interactions. They do not significantly penetrate the membrane hydro-
phobic interior although they may exhibit some weak hydrophobic interaction. Peripheral
proteins can be readily removed from the membrane by simply altering the ionic strength
of the media or adjusting the pH. The removed protein is freely soluble in water. Integral
proteins penetrate the membrane hydrophobic interior to varying extents and so can only
be removed from the membrane by far more drastic measures. Integral proteins can only
be removed by destroying the membrane and the removed protein is isolated as water-
insoluble aggregates. While classifying proteins as either peripheral or integral is easy and
not subject to much controversy, it is not very satisfying as most membrane proteins fit
into the integral class. In this topic, membrane proteins will be classified primarily by the
extent and nature of their hydrophobic interactions with membranes. As more is discovered
about membrane proteins, devising a meaningful classification system becomes ever more
challenging. Overlaps between classes are all too common. Although certainly not perfect,
the membrane classification system outlined in Table 6.4 will be employed. This system is
an expansion of that proposed for membrane proteins by Robert Gennis in his 1989 topic Bio-
membranes: Molecular Structure and Function [1] .
I. Peripheral Proteins
Peripheral proteins are held to the membrane surface primarily through electrostatic or
hydrogen bonds [6] . They can be divided into two basic types; those that are attached
TABLE 6.4 Membrane Protein Classification System.
I. Peripheral
A. Bound to Protein
B. Bound to Lipid
II. Amphitropic
III. Integral
A. Endo and Ecto
B. Trans-membrane
Type I: Single trans-membrane a -helix
Type II: Multiple trans-membrane spans by a -helices
Type III: Membrane domains of several different polypeptides assemble to form a channel through the
membrane
e b -barrels
IV. Lipid-Linked
A. Myristoylated
B. Palmitoylated
C. Prenylated
D. GPI-linked
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