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

J. Dohnálek¹, P. Kolenko¹, T. Skálová¹, J. Hašek¹, O. Vaněk^2,3, D. Rozbeský^2,3, K. Kotýnková³, P. Novák³, K. Bezouška^2,3

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

dohnalek007@gmail.com

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.