16.3: Membrane Proteins

Of course, membrane proteins themselves have domains. These provide catalytic and other activities inside and outside of cells and organelles, and keep them attached to the membrane. Like phospholipids, membrane proteins are amphipathic, with hydrophobic domains that noncovalently interact strongly within the fatty-acid interior of membranes. Some integralmembrane proteins span the entire membrane, with hydrophilic domains facing the cytosol or cell exterior. Peripheral proteins bind to a membrane surface through noncovalent interactions. Different membrane proteins are shown in Figure 16.13.

Figure 16.13: Integral-membrane proteins may penetrate or span the membrane; also shown are peripheral proteins and lipoproteins.

286-2 Domains of Membrane Proteins

CHALLENGE

Count and identify specific or generic functional domains in the proteins in Fig 16.13.

Hydrophobic amino acids of membrane proteins are organized into functional regioons. These consist of one or more nonpolar alpha-helical domains that interact with the fatty-acid interior of the membranes. Hydrophilic domains tend to have a more tertiary structure. These domains face the aqueous cytosol and cell exterior. Two transmembrane proteins are cartooned in Figure 16.14.

Figure 16.14: Integral transmembrane proteins cross the membrane one or more times.

The protein on the left in Figure 16.14 crosses the membrane once, while the one on the right crosses the membrane three times. Regardless of the number of times a polypeptide crosses the membrane its C-terminus always ends up on the extracellular surface of the cell.

CHALLENGE

Can the N-terminal amino acid of a plasma membrane polypeptide ever face the outside of a cell?

Alpha-helical domains that anchor proteins in membranes are mostly nonpolar and hydrophobic themselves. For example, consider the amino acids in the alpha-helical domain of the red blood cell–membrane protein glycophorin A, a protein that prevents red blood cells from aggregating or clumping in the circulation. One glycophorin A polypeptide with its hydrophobic transmembrane alpha helix is cartooned in Figure 16.15 (below).

Figure 16.15: Hydrophobic amino acids in glycophorin form a helix spanning a red blood cell plasma membrane.

Glycophorin A monomers pair to form dimers in the plasma membrane (not shown above). Proteins that span membranes multiple times may include amino acids with charged polar side chains, provided that these side chains interact between helices, so that they are shielded from the fatty acid environment in the membrane. Because of these hydrophilic interactions, such proteins can create pores for the transport of polar molecules and ions. (We’ll see some of these proteins later).

Integral membrane proteins that do not span the membrane also have a hydrophobic helical domain to anchor them in the membrane, while their hydrophilic domains typically interact with intracellular or extracellular molecules that can hold cells in place, give cells and tissues their structure, and the like.'The very presence of hydrophobic alpha-helical domains in transmembrane proteins makes them difficult if not impossible to isolate from membranes in a biologically active form. But the peripheral polypeptide cytochrome c readily dissociates from cristal membranes, making it easy to purify. The inability to purify other biologically active cristal membrane electron carriers is what slowed our understanding of the structure and function of the mitochondrial electron transport system.

CHALLENGE

How was this problem solved? Find the answer in an earlier chapter!

It is possible to determine the primary structure of a polypeptide encoded by a gene before the protein itself has been isolated. Just by knowing the DNA sequence of a gene, we can infer the amino acid sequence of the protein encoded by the gene.

Then we can identify all of the hydrophobic amino acids in the inferred sequence and generate a hydrophobicity (or hydropathy) plot, such as the one in Figure 16.16.

Figure 16.16: Hydropathy plots correlate amino acid hydrophobicity with its position in a polypeptide. Long regions of hydrophobic amino acids suggest a possible membrane-protein domain.

The protein in this hypothetical example has two regions, or domains of hydrophobic amino acids. They are identified as stretches of uninterrupted hydropathy (hydrophobicity) above the 0 level along the X-axis. The protein shown here is probably a transmembrane protein. To see how a hydropathy plot can predict whether a protein is a membrane protein, check out the following link.

287-2 Hydropathy Predicts Hydrophobic-Membrane Protein Domains