Major prion protein 1 precursor
Bos taurus (bovine)
In the early days of the Protein Data Bank (PDB) all of the deposited, experimentally determined, 3-dimensional structures were contributed by protein crystallographers. They were determined by the diffraction of x-rays from crystals of the protein. Sometimes however it may be difficult or impossible to obtain crystals of a protein. In the past this meant that the structure of such a protein remained unknown. Recently however another technique, nuclear magnetic resonance or NMR, has become available for the determination of protein structures. The successful application of NMR to this kind of investigation is largely based on the pioneering work of Kurt Wuethrich and for his contributions he was awarded the 2002 Nobel prize in chemistry. Molecules can be studied by NMR while in solution. The effect that is observed is the resonance of a external magnetic field with the protons in the nuclei of atoms. New developments in methodology and stronger magnetic fields have made it possible to study larger and larger molecules by this technique. One important application of this technique has been the determination of the structure of the prion protein. Prusiner (Nobel prize in medicine, 1997) had discovered that the infectious agent for certain kinds of diseases like bovine spongiform encephalopathy (BSE or mad cow disease) in cows or the Creutzfeldt-Jacob disease in humans is a protein. That was a highly unusual discovery: never before had a protein been shown to be infective. It is therefore of great interest to understand the reasons for this infectivity in detail, particularly because the disease causing properties of this protein seem to be related to the details of its structure.
The structure shown here is that of bovine prion. It is globally very similar to other known (also by NMR) prion structures, from mice, Syrian hamsters and humans. It consists a compact globular core of about 100 residues, preceded by an almost equally long, but very flexible N-terminal protein tail. It is shown that the globular core at the C-terminus is very similar to the corresponding domain of the human prion protein.This explains how cow meat, which is an important part of the daily diet in many country, can affect humans, if the cow from which the meat is obtained, suffers from BSE. Further details on this disease can be found under entry xPSSS:1QLX which describes the NMR structure of the human prion protein.
Protein Data Bank (PDB)
author: Arno Paehler