The molecular puzzle of C-type lectin like natural killer cell receptors


J. Dohnálek1, P. Kolenko1, T. Skálová1, J. Hašek1, O. Vaněk2,3, D. Rozbeský2,3, K. Kotýnková3, P. Novák3, K. Bezouška2,3


1Institute of Macromolecular Chemistry, v.v.i., Academy of Sciences of the Czech Republic, Heyrovského náměstí 2, 16206 Prague 6, Czech Republic

2Department of Biochemistry, Faculty of Science, Charles University in Prague, Hlavova 8, 12840 Prague 2, Czech Republic

3Institute of Microbiology, v.v.i., Academy of Sciences of the Czech Republic, Vídeňská 1083, 14220 Prague 4, Czech Republic


Natural killer cells belong to the innate immune system and are able to recognize and destroy virus-infected or tumour cells [1]. Apart from immunoglobulin-type receptors these cytotoxic lymphocytes utilize a row of cell surface C-type lectin like (CTL) molecules involved either in activation or inhibition of the NK cell response which results in release of perforin and granzymes and lysis of a target cell within minutes. In mammals the number of types of CTL receptors identified for individual species differs while the overall architecture of such a receptor is relatively constant. An intracellular part responsible for signaling is connected via a transmembrane linker (helix) to an extracellular domain involved in receptor-ligand or cell-cell interactions. Several studies confirmed that the interacting partners for these receptors are again cell surface proteins of the same type (Clr – C-type lectin related in rodents or human LLT1 – Lectin-like transcript-1) [2]. Structural details underlying the functionality of these receptors and especially formation of these protein-protein complexes are still only sparse. Our recent work has been focused on mouse and rat receptors and ligands of the NKR-P1 family (CTL type). Three-dimensional structures based on x-ray diffraction analysis of mouse NKR-P1A and Clrg complemented by a high resolution structure of human CD69 together with sequence analysis of the protein family give first indications of their specific properties [3].  The surface loop of the CTL domain fold may play an important role in receptor-ligand interactions and amino acid sequence analysis leads to predictions of similar behaviour within the NKR-P1 family.

1. E. Vivier, E. Tomasello, M. Baratin, T. Waltzer, S. Ugolini, Nat. Immunol.  9, (2008), 503.

2. J.R. Carlyle, A.M. Jamieson, S. Gasser, C.S. Clingan, H. Arase, Proc. Natl. Acad. Sci. USA 101, (2004), 3527.

3. P. Kolenko, T. Skalova, O. Vanek, A. Stepankova, J. Duskova, J. Hasek, K. Bezouska, J. Dohnalek, Acta Crystallogr. F 65, (2009), 1258.


Funding by the E. C. in Integrated project SPINE2-Complexes, no. 031220, and through ELISA grant (226716, synchrotron access, projects 09.1.81077 and 09.2.90262), by Ministry of Education of the Czech Republic (MSM 21620808), and by the Czech Science Foundation (303/09/0477, 302/11/0855 and 207/10/1040) is gratefully acknowledged. The authors wish to thank Uwe Müller for support at the beam line BL14.1 of Bessy II,  Helmholtz-Zentrum Berlin, Albert-Einstein-Str. 15 and Institute of Biotechnology ASCR for access to the X-ray diffraction suite.