Structures of receptors and ligands of mammalian NK cells

Tereza Skálová¹, Kristýna Kotýnková, ^2,3 Petr Kolenko⁴, Jarmila Dušková¹, Tomáš Kovaľ⁴, Jindřich Hašek^1,4, Ondřej Vaněk, ^2,3 Jan Stránský¹, Karla Fejfarová⁴, Jan Dohnálek^1,4

¹Institute of Biotechnology, Academy of Sciences of the Czech Republic, v.v.i.,

Nad Safinou II, 366, 252 42 Vestec, Czech Republic,

²Department of Biochemistry, Faculty of Science, Charles University Prague, Hlavova 8, 128 40 Praha 2, Czech Republic,

³Institute of Microbiology v.v.i., Academy of Sciences of Czech Republic, Vídeňská 1083, 142 20 Praha 4, Czech Republic,

⁴Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic, v.v.i., Heyrovského nám. 2, 162 06 Praha 6, Czech Republic,

t.skalova@gmail.com

Natural killer cells (NK cells) are large granular lymphocytes, a sort of lymphocytes discovered in the early 1970s. They comprise ca. 10 % of lymphocytes. They are able to kill virally infected and tumor cells. Unlike T-cells, the activity of NK cells is innate, they do not need to have previous experience with a tumor – they are natural killers.

We solved an X-ray structure of an extracellular part of mouse Clr-g [1], a ligand for NK receptor NKR-P1F. The diffraction data of a rod-like crystal were measured at synchrotron BessyII of HZB in Berlin and processed up to 1.95 Å. The protein forms dimer similar to that of CD69.

The dimer differs slightly from CD69 dimer in mutual orientation of both monomers. This effect was observed also for other similar protein dimers and seems to be an effect of flexibility of the dimers and not a characteristic of the dimerization mode of the protein.

A model of a complex with its binding partner, NKR-P1F, was designed based on electrostatic complementarity of both molecules. In this model, the complex is not formed in “face to face” mode, as is usually expected; rather the dimer of NKR-P1F embraces one of the monomers of Clr-g.

This work was supported by the Czech Science Foundation (grant No. P302/11/0855), Ministry of Education, Youth and Sports of the Czech Republic (grants LG14009 and EE2.3.30.0029) and by the project BIOCEV CZ.1.05/1.1.00/02.0109 from the ERDF.

[1] Skalova et al., J. of Immunology, 2012, 189 (10), 4881-4889.