Classical protein structure with new qualities discovered
Researchers at the Charité – Universitätsmedizin Berlin discovered, in cooperation with scientists at the Max Delbrück Centrum, the Free University Berlin and the Beckman Research Institute in California, a protein within the immune system of the chicken, which appears to enhance its body's defences. "It exhibits the structure of classic defense molecules, such as those of humans. But unlike comparable molecules in other mammals, it is capable of recognising fats - so-called lipids - instead of protein fragments”, explains Prof. Andreas Ziegler, the director of the Institut für Immungenetik of the Charité. In the current issue of the prestigious scientific journal "PloS Biology"*, he and his colleagues demonstrate that the immune system of the chicken is still full of surprises.
A common feature of the immune system of all vertebrates is the presence of the so-called major histocompatibility complex (MHC). The MHC produces a group of molecules that are responsible for the distinction between exogenous (foreign) and endogenous (“self”) substances. They have the task of reporting foreign protein fragments, so-called peptides, that may be derived from viruses or bacteria within an infected cell, to the immune system. Peptides dock unto a specific site of the MHC molecule. As a result, this molecule transports the captured peptide to the cell surface and presents it to immune cells such as T-cells. If these recognize the peptide as “foreign”, a series of reactions is initiated that may end up with the destruction of the infected cell.
The MHC genes of the chicken are divided into two regions (MHC-B and MHC-Y) on the same chromosome. The MHC-B region has similarity to the MHC of mammals, but it is much smaller. Nevertheless, the products of these genes have the typical structure of classical MHC molecules with a binding site for peptides. The team led by Prof. Ziegler examined the structure and binding properties of a protein (YF1*7.1) from the MHC-Y region. Using X-ray crystallography, a technique that permits to determine the molecular structure of a protein, it was first shown that the YF1*7.1 molecule possesses the characteristic structure of classical MHC molecules. However, it has an atypical binding site which binds lipids, but not peptides. This ability has been known up to now only from certain "non-classical" MHC class I proteins, in particular CD1 molecules.
Therefore, the binding of lipids to the YF1*7.1 protein closes the gap that separated classical from non-classical MHC class I molecules, at least in structural terms and with regard to the type of binding partner. YF1 proteins interacting with lipids may serve the chicken to increase its seemingly very narrow repertoire of peptide- or lipid-binding MHC molecules in comparison to that of mammals and may thus help this species to efficiently protect itself from a variety of pathogens.
* Chee Seng Hee et al.: Structure of a Classical MHC Class I Molecule That Binds “Non-Classical” Ligands. In: PLoS Biology. 07 Dezember 2010. DOI 10.1371/journal.pbio.1000557
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