Looking at Protein Structures

Some of the recent protein structures to come out of the work of people at the University of Oxford Laboratory of Molecular Biophysics are described here. For each structure, you can either view a bigger image, or use the icon to download the coordinates and view with a program like Rasmol. For an explanation of the parts of protein structures click here.

Protein Kinase

Phosphorylase kinase is a member of a family of proteins known as protein kinases. Members of this class of proteins control all the major events in a cell's life and as such are becoming important targets of drug design. Protein kinases alter cellular processes by sticking phosphate labels on specific residues of the proteins that drive those processes.

If you look carefully at the structure you can see that it has two distinct portions joined by a hinge - it looks a bit pacman! One half is made mostly from helices and the other from strands. The protein to which they add the phosphate group sits between the two halves of the kinase - in pacman's mouth!

Protein Phosphatase

Protein Phosphatase is the other half of the double act formed by the protein kinases and the protein phosphatases. Where kinases stick phosphate labels on proteins, phosphatases rip them off again. Between them they control the important activites in a cell's life, like when to divide into two new cells and when to make new proteins. When these processes go wrong a variety of diseases can occur, including cancers. The structure has a big sheet made of strands which lies at the centre and is surrounded by helices. At first sight, it is not unlike the kinase structure. This phosphatase only acts on amino acids called "tyrosine".

This phosphatase is one of the recent successes of structure prediction.

SH2 Domain

Sometimes, the job of a phosphate label is to act as a signal that various actions in the cell should be started. A phosphate label on a protein at the surface of the cell is often the signal that a cell should become active and start dividing. SH2 domains recognize proteins which are carrying a phosphate label on a tyrosine amino acid, and so begin the pathway that leads to the activation of the cell. Many different proteins have SH2 domains, so that signalling pathways are more often signalling networks.

SH3 Domain

SH3 domains are little "molecular adaptors". Their job is to bind to runs of proline amino acids in other proteins. A protein which contains an SH2 domain and an SH3 domain can serve to bring together two proteins: one which contains a phosphate labelled tyrosine, and one which contains a stretch of prolines.

Viral Neuraminidase (Sialidase)

Garry Taylor, Elspeth Garman, Robert Webster and Graeme Laver.

This protein helps baby `flu viruses escape from the parent cell. It sticks out of the virus surface, on a stalk and from one angle looks like a six-bladed propellor. New strains of `flu have slightly different versions of this protein, but the functional area stays identical between the types. There is a model of the whole virus next door.

Suc 1

Suc1 is a small protein that is involved in controlling cell division. It is believed to interact with the protein kinase which decides whether or not a cell should divide.