Bovine beta-Lactoglobulin

When we take a closer look to the skeleton of this protein, underneath the protein surface, we can see that it is a single chain that is folded in a very defined way, with all kinds of regularities in the fold, called secondary structures. For example we have here a series of up and down arrows that represent beta-strands, which are organized in planes, called beta-sheets. These beta-strands are aligned in such a way that there is an optimal hydrogen-bonding between adjacent strands, providing a lot of stability to the global fold.

There is another property that gives this molecule structural integrity. This integrity is provided by these green humps, indicating covalent bridges. The molecule has two of such covalent bridges between sulfhydryl groups that are at different parts of the chain. Such covalent bonds lock the structure in a particular fold. Actually, underneath this twisted structure, there is an additional third sulfhydryl group that is very reactive. This can not be seen, since it is covered by the structure.

OK, look now at to the chemical function of the amino acids in this chain. Lets first zoom in to take a closer look at the interior of the protein. In lila we see all kinds of non-polar residues in the core of the protein. They try to avoid interaction with water. In yellow you we see all kinds of aromatic residues, for example tyrosine and tryptophan. These are generally still buried, but a bit more on the outside. And finally we can see residues that are encoded blue or red representing positive and negative charged residues. Clearly, most of these residues are on the outer surface of the protein. However, on one side there is one charge sticking out, this is the dimer-interface. The global fold together with and the large variety of chemical appearances make working with this protein challenging and sometimes troublesome.

Collagen tripeptide

The three chains are wound around a common axis. In the core, only the smallest amino acid in nature can be accomodated, namely glycine, which contains only a hydrogen atom instead of a bulky side chain. Strictly, every third amino acid is a glycine and is present in the core of the triple helix.

In the core you can see the blue-colored residues. All other amino acid side groups point outward, especially the bulkier side groups just following the glycines in the polypeptide chain. The periferal residues, depicted in other colors, are for example involved in the crosslinking of collagen, and can be used for chemical modification of collagen.

The helix structure is stabilized by hydrogen bonds between the peptide backbone CO- and NH-groups, and by the presence of many proline and, especially, hydroxy proline residues. The hydrogen bonds are indicated by the white dotted line. You can also easily find the pentagonal ring structure of the prolines and the red-colored hydroxy groups of the hydroxyprolines in this picture.

Water molecules, which are represented in this movie by their red-colored oxygen atoms, are closely associated with the triple helix. They may play a role in helix stabilisation. In addition to water, you can see a few cosolvent molecules, which were used to prepare the crystal.

You can still clearly see the proline and hydroxyproline rings, which are not perfectly flat, but puckered up and you can see that each chain forms its own, left handed helix with three amino acids per turn (each third amino acid close to the core of the triple helix).

°pdb 1bkv = T3-785 (Kramer RZ, Bella J, Mayville P, Brodsky B, Berman HM(1999) Nature Struct Biol 6: 454-457)