Membrane Proteins

Transmembrane 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.

Multi-membrane-spanning proteins

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.