Structural properties of NK receptors and ligands with C-type lectine-like fold

T. Skálová¹, P. Kolenko¹, J. Dušková¹, T. Kovaľ¹, J. Hašek¹, J. Stránský^1,2, J. Dohnálek¹

¹Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic,

v.v.i., 16206 Praha 6, Czech Republic

²Faculty of Nuclear Sciences and Physical Engineering, Czech Technical University, Břehová 7, 115 19 Praha 1, Czech Republic

t.skalova@gmail.com

Natural killer cells (NK cells) are blood corpuscles, more precisely, a sort of lymphocytes. They comprise 5-10% of lymphocytes in blood and their role in the immune system is to discover and kill cancer cells and cells infected by viruses.

This work is aimed at a class of NK receptors, i.e. receptors on the surface of NK cells, which have a special fold: C-type lectin-like fold (CTL fold, (1)). More generally, other receptors, not only NK receptors, but with CTL fold, will be mentioned included in the presented analysis. The role of NK receptors with CTL fold is to mediate contact with other cells, in order to kill infected or cancer cells. NK receptors with CTL fold interact with protein ligands, which are of the same, CTL, fold, and are located on surface of partner cells.

During recent years, we have solved structures of several receptors/ligands with CTL fold (high resolution structure of human CD69 (2), mouse NKR-P1A (3, 4), mouse Clr-g (5)), and other structures are in progress. These structures inspire us to study 1) CTL fold, its characteristics and its variability, 2) Types of oligomerization of CTL receptors and ligands (Figure 1), and 3) Rules of formation of CTL receptor-ligand complexes.

It was found that the dimerization mode of CTL proteins is very variable, while complexation of structurally known CTL protein-protein complexes happens in the same area of monomers, in the part distant to N and C terminal region.

Figure 1. Comparison of dimerization modes of three mouse CTL proteins: NK receptor NKR-P1A (PDB code 3M9Z), NK receptor Klrg1 (3FF9), and a ligand for NK receptor NKR-P1F: Clr-g (3RS1).

This work was supported by the Czech Science Foundation (P302/11/0855), and the Ministry of Education, Youth and Sports of the Czech Republic (CZ.1.07/2.3.00/30.0029).

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