Membrane Proteins
Membrane proteins are either extrinsic or intrinsic. Extrinsic membrane
proteins are entirely outside of the membrane, but are bound to it by weak
molecular attractions (ionic, hydrogen, and/or Van der Waals bonds).
Intrinsic membrane proteins, the class we are mainly interested in, are
embedded in the membrane. Many of them extend from one side of the membrane
to the other and are referred to as transmembrane proteins.
Cells are constantly pumping ions in and out through their plasma
membranes. In fact, more than half the energy that are bodies consume
is used by cells to drive the protein pumps in the brain that do nothing
else but transport ions across plasma membranes of nerve cells. How can
ions be transported across membranes that are effectively impermeable to
them?
Cells contain proteins that are embedded in the lipid bilayer of their
plasma membranes and extend from one side of the membrane through to
the other. Such transmembrane proteins can function to effect ion
transport in several ways. But how can they cope with the energetically
highly unfavorable situation in which an ion must pass through the
hydrophobic inner layers of the plasma membrane?
If we examine the detailed structures of many transmembrane
proteins, we see that they often have three different domains, two
hydrophilic and one hydrophobic. A hydrophilic domain (consisting of
hydrophilic amino acids) at the N-terminus is poking out in the
extracellular medium, a hydrophobic domain in the middle of the amino
acid chain, often only 20-30 amino acids long, is threaded through the
plasma membrane, and a hydrophilic domain at the C-terminus protrudes
into the cytoplasm. The transmembrane domain, because it is made of
amino acids having hydrophobic side chains, exists comfortably in the
hydrophobic inner layers of the plasma membrane. Because these
transmembrane domains anchor many proteins in the lipid bilayer,these
proteins are not free-floating and cannot be isolated and purified
biochemically without first dissolving away the lipid bilayer with
detergents. (Indeed, much of the washing we do in our lives is necessitated
by the need to solubilize proteins that are embedded in lipid membranes
using detergents!)
For reasons that are not well understood, many transmembrane
proteins are glycoproteins in the sense that sugar side chains are covalently
attached to their hydrophilic domains that protrude into the extracellular
membrane. A typical mammalian cell may have several hundred distinct
types of glycoprotein studding its plasma membrane. Each of these
glycoproteins will have its extracellular domain glycosylated with a
complex branching bush of sugar residues covalently linked to the
asparagine side chains. Some glycoproteins may have 2 or 3 asparagine-
linked sugar side chains, others may have dozens.
An elaboration of this scheme
depicting membrane proteins having single transmembrane domains
involves certain membrane proteins that have multiple transmembrane
domains. As one scans along the amino acid sequence of these proteins, it
becomes apparent that hydrophilic domains (i.e. having hydrophilic amino
acids) alternate with hydrophobic domains. The protein chain as a whole
when embedded in the plasma membrane actually weaves back and forth
between opposite sides of the plasma membrane. Some think such proteins
have the configuration of snakes and hence term them serpentine
membrane proteins. A commonly used type of structure seen in many
hundreds of serpentine transmembrane proteins involves 7 hydrophobic
domains inserted into the plasma membrane separated by hydrophilic
regions that are looped out alternatively into either the cytoplasm or the
extracellular space.