Membrane proteins and their sugars

Membrane proteins also begin at the ER. On the way to their destinations, many of them pick up sugar chains that help cells recognize one another and protect the proteins themselves.

Threading proteins into the ER membrane

A ribosome builds each protein as a chain of amino acids called a polypeptide. As Chapter 4 described, short stretches of the chain act as sorting signals, like address labels telling the cell where the protein belongs. Most transmembrane proteins carry a label that sends the ribosome and its growing chain to the ER membrane: the ER signal sequence. (The main exceptions are proteins headed for mitochondria and chloroplasts.)

Once the chain reaches the ER, its amino acid sequence decides which parts stay in the membrane:

About 20 amino acids in a helix is just long enough to span the membrane. A chain with one such stretch crosses the membrane once, and each additional stretch adds another transmembrane segment, so the protein weaves back and forth like a thread stitched through cloth.

Computer programs use this rule in reverse: they scan a protein’s amino acid sequence for such hydrophobic stretches to predict whether it’s a transmembrane protein. Each prediction still has to be confirmed by experiment.

Glycosylation

Attaching a carbohydrate to a lipid or a protein by a covalent bond is called glycosylation. It produces the glycolipids and glycoproteins found in membranes. In the plasma membrane, their sugar chains face the outside of the cell, where they serve two main purposes:

• Recognition. Cells identify one another by the carbohydrates on their surfaces. As an animal embryo develops, sheets of cells slide past one another to build organs and the spinal cord, and each cell finds its place by recognizing the sugars on its neighbors.
• Protection. Some animal cells wear a sugar-rich coat that cushions them against physical damage. A glycoprotein’s own sugar chains also guard it against harsh conditions outside the cell, including proteases, enzymes that digest proteins.

Proteins are glycosylated in two places, the ER and the Golgi apparatus, and in two different ways, each named for the atom the sugar attaches to.

N-linked and O-linked glycosylation

In the ER, sugars attach to a nitrogen atom (N) in the side chain of the amino acid asparagine. This is N-linked glycosylation, and it also occurs in archaea. It’s common on membrane proteins bound for the cell surface.

The sugars for N-linked glycosylation arrive prebuilt. First, a branched group of 14 sugars, called an oligosaccharide or carbohydrate tree, is built on a lipid in the ER membrane. Then an enzyme, oligosaccharide transferase, moves the whole tree onto an asparagine in the polypeptide.

In the Golgi apparatus, and only there, a string of sugars is added to an oxygen atom (O) in the side chain of serine or threonine. This is O-linked glycosylation.

In animals, O-linked glycosylation produces heavily sugar-coated proteins that cells secrete, called proteoglycans. Proteoglycans help organize the extracellular matrix, and they’re part of mucus, which coats many cell surfaces and is released into saliva and other fluids. All that carbohydrate is what makes mucus slimy.

Check yourselfA polypeptide has three separate stretches of about 20 hydrophobic amino acids. What would you predict about the finished membrane protein?

It would have three transmembrane segments, crossing the membrane three times. Each hydrophobic stretch folds into an α helix that stays in the nonpolar core of the bilayer.

Check yourselfA protein carries sugars attached to a serine. Which kind of glycosylation is this, and where in the cell did it happen?

O-linked glycosylation, because the sugars are bonded to the oxygen in serine’s side chain. It happened in the Golgi apparatus, the only place O-linked glycosylation occurs.