Four amino acids as a starting point for gripper proteins
Clamping mechanism for microtubules of the cytoskeleton clearedRead out
The microtubules of the cytoskeleton separate the chromosomes from one another during cell division or transport cell organelles and vesicles with substances to their destination. How they always find the right docking point, was so far unclear. Now scientists have identified a sequence of four amino acids as the crucial marker at the end of the microtubule. Their results have now been published in the journal "Cell".
A living cell is traversed by a dense network of polymer fibers. The three types of these fibers traverse the cell and together form the cytoskeleton, whose job it is to stabilize the cell and keep it in shape. The polymer fibers, however, do not form a stiff scaffold, but react flexibly to external influences and are actively involved in numerous vital processes in the cell. Thus, the ends of certain polymer fibers, the microtubules, chromosomes, cell organelles, and other cell constituents can specifically recognize and bind with them.
Responsible for this are special proteins that act like grippers - they dock with one end to the fiber, with the other they hold the specifically recognized cell component. The different gripper proteins are very different and complicated - and all have in common that they can connect to the fiber end.
Four amino acids lined up
A particularly member of this class of claw proteins is the protein EB1, which is the only one that can dock directly to the ends of the microtubules. All other proteins can only bind to the EB1. It has long been unclear how EB1 and the other proteins find each other. This question is now answered by the results of researchers from Paul Scherrer Institute and Erasmus Medical Center.Using the amino acid sequence SxIP (colored), proteins can dock tightly to the protein EB1 and thus to the ends of the microtubules. Paul Scherrer Institute (PSI)
The researchers were able to show that there is a very small section common to all these proteins, allowing them to hook onto the fiber end. This section works like a ticket - who has it can ride on the fiber end. They were able to show that all these proteins share a particular sequence of four amino acids. display
This sequence has a typical shape that fits exactly in a free space in the structure of the EB1. Thus, regardless of their other form, the proteins can dock exactly to the EB1 and thus indirectly to the ends of the microtubules. In the usual nomenclature, this sequence is abbreviated SxIP, where S is the amino acid serine, I is isoleucine, and P is proline; x stands for any other amino acid.
New drugs possible
"Because microtubules are involved in almost all processes in the cell - including the separation of chromosomes during cell division - they are also a central target for drugs that block the growth of cancer cells. Our results may help to develop new drugs targeted into microtubule cellulosic processes
intervene. "explains Michel Steinmetz, head of the working group Protein Interactions at the Paul Scherrer Institute and initiator of the project, on the possible application of his results.
The results of the research were first made possible by a combination of methods - the three-dimensional structure of the participating proteins was investigated and their amino acid sequences screened for common sections. Finally, it was clearly demonstrated that the proteins
can no longer bind to the microtubule ends via EB1 as soon as the SxIP sequence is damaged. At the Paul Scherrer Institute, the overall concept of the research project has been developed and the structural investigations by means of X-ray crystallography have been carried out at the synchrotron light source Switzerland SLS of the Paul Scherrer Institute.
In addition to researchers from the Paul Scherrer Institute and the Erasmus Medical Center, scientists from the Institute of Molecular Biology of the ETH Z rich and the Biochemical Institute of the University of Zurich were involved in the work.
(Press release Paul Scherrer Institute (PSI), 27.07.2009 - NPO)