Opening Image: Crystal structure of the yeast proteasome core, referred to as the 20S proteasome (named according to its sedimentation coefficient). The core, which consists of 28 subunits arranged in four rings, is conserved from bacteria to mammals. Fourteen of the subunits in the proteasome core are proteases, or enzymes that hydrolyze proteins into peptides. Proteins targeted for proteasome degradation include misfolded or nonfunctional proteins, as well as many normal, though short-lived, proteins. One class of proteasomes process intracellular antigens for presentation to the immune system.

Outline

1. Quaternary Structure
2. Van der Waals Contacts
   1. Definition
   2. In a Dimer

The quaternary structure imparts structural and functional credibility to proteins. Between one-half and two-thirds of known structures are multimeric. Most complexes contain four subunits or less, and the large majority are homomeric. In addition, there is a strong tendency for symmetry in complexes, even for heteromeric complexes.

The shape of dimer-binding sites is often but not always relatively flat. Interfaces are frequently largely hydrophobic. Although there are other hydrophobic patches on the surface, the stability of the dimer stems from both fit (shape) and electronic (hydrogen bonding, charge interactions) complementarity at the subunit interface. Structurally conserved residues distinguish between binding sites and exposed protein surfaces.

Van der Waals Contacts

Operational Definition

How do we define contacts between two protein molecules? We simply ask the computer to search for atoms in one molecule or subunit which are close enough to maintain van der Waals interactions with atoms in the adjacent subunit. Since van der Waals or dispersion forces are very short range, the cutoff distance for significant interaction between atoms is the sum of the van der Waals radii plus 0.5 Å. That means any visible spaces between the contact surfaces of the dimer are less than 0.5 Å.

Van der Waals Contacts

In a Dimeric Protein

We can show the regions which comprise contact surfaces by using different colors in the model. To show you how this looks, let's examine human defensin HNP-3, one of the smallest dimers in the Protein Data Bank (PDB). The monomer has 30 amino acid residues and folds into a unique tertiary structure. When the monomers meet, they associate to form a dimer. The interactions that stabilize the dimer include van der Waals forces at the region where the two subunits fit together. The molecule consists of two identical chains, A and B.

Toggle spacefill. The oxygen atoms of the ordered water molecules are shown in dark blue to distinguish them from the oxygen atoms of the peptide. Most of the ordered water molecules are hydrogen bonded to peptide carbonyl oxygen atoms or –NH groups.

Click here to learn more about defensins.

Surface model of the dimer. Remove one of the monomers for a view of the interface. The contact residues at the interface are shown in lighter shades. Remember that the cutoff distance for significant van der Waals interaction between atoms is the sum of the van der Waals radii plus 0.5 Å. That means any visible spaces between the contact surfaces of the dimer are less than 0.5 Å. As you can see, the two surfaces fit together fairly closely. In other words, the defensin monomers meet one criterion for binding to each other, namely, shape complementarity -- the most basic ingredient of molecular recognition. We'll explore other criterion in later lectures.

Isolate the interface to see the van der Waals contacts between the subunits. The contact surfaces are relatively flat and fit together nicely.