Apoptosis inhibitor BCL-XL
Homo sapiens (human)
In living organisms new cells are created and old cells destroyed on a continuous basis. When cells are supposed to die, they are chemically marked to do so. This process is known as apoptosis or programmed cell death. Sometimes cells can become immortal. They are not destroyed and together with the growth of additional new cells they form tumors. The resulting diseases are generally known as cancers. Apoptosis obviously is a process that must be carefully orchestrated to make sure that the balance of cell growth and death is well kept.
One protein that is involved in the regulation of programmed cell death is the protein shown here. It has a compact core composed mainly of alpha-helices but in between, connecting the first and the second helix in the structure, a long piece of polypeptide that is not well ordered. The structure has been determined by a combination of two independent techniques, x-ray crystallography and nuclear magnetic resonance (NMR). While this long disordered loop cannot be seen in the x-ray structure, it can be seen by NMR. How the protein works is not well understood and it is hoped that the knowledge of structure will help to understand its mode of action better. When the structure is compared to other known structures one finds that it has some similarity with one part of diphtheria toxin. Its structure is similar to the so-called membrane translocation domain of diphtheria toxin, whose function is to open a channel through the membrane. It is thought that bcl-xL has such a function: to form pores in the membrane, holes through which ions can flow from the interior of the cell to the exterior and vice versa. This may help to balance electrochemical gradients that are normally present as a result of the membrane preventing free flow.
Protein Data Bank (PDB)
author: Arno Paehler