Hašek Jindřich1, Skálová Tereza1, Kolenko Petr2, Dušková Jarmila1, Koval Tomáš2, Fejfarová Karla2, Stránský Jan1, Dohnálek Jan1,2

1Institute of Biotechnology AV ČR, Vídeňská 1083, 14 220 Praha 4,

2Institute of Macromolecular Chemistry AV ČR, Heyrovského nám.2, 16206 Praha 6



Natural killer cells indispensable for innate immunity are in the center of very complex machinery of interactions between cell receptors and ligands ensuring signal transduction, recognition, etc. They have also complex mechanisms for activating the adaptive immune system. The resulting effect depends on numbers of cellular receptors expressed on the NK-cells, on the numbers of receptors on the surface of other the immune and the tissue cells in neighborhood, on a type of their clustering and on concentration of small and high molecular weight ligands secreted into the surrounding intercellular space. Thus, the immune response is always a complex interplay of many events. Intensity of response usually depends on clustering of receptors, on attachment of ligands on the intracellular side of receptors, and on number and strength of interactions with extracellular ligands. Moreover, cells perceive more signal pathways, some acting in synergy, some against each other. The Table presented on poster may help to get a brief glimpse on complexity of the problem.


Main reason for joining the protein crystallography data with data provided by other biophysical methods is to get the 3D view of the intermolecular interfaces, which seems to be very useful for a rational design of medical treatment. Advantages of crystallography of protein complexes are namely in (a) visualization of intermolecular interaction modes (it allows controlled intervention into the immunological processes and thus a rational modulation of functions), and (b) in the fact that the inspected proteins are under similar stress as in the tissue (protein concentrations in “crystals” are similar to those in the tissues). Protein crystallography helps in:

·         elucidating the detailed mechanism of adhesion and signal transmission between cells,

·         reliable confirmation of reasons why molecular partners responsible for immunological processes bind,

·         visualization of the interface provides a basis for a rational variation of the process under study .


Regrettably, the 3D structure data and snapshots of the complexes with their interaction partners are very sparse by now. Thus, the review of NK-cell receptor interactions is intended namely for rational planning of the future experiments research in the field. Protein crystallography is a relatively slow tool, and thus a rational selection of a research targets is very important.


The summary of the NK-cell surface receptors shows a large pool of the NK-cells receptors and their interactions with hundreds of their ligands. The Table summarizes the available biochemical data on the biomolecular interaction partners /9,11,12 etc./ and mixes them with the structure data obtained by X-ray crystallography /10/.


The NK-cell receptors are sorted according to their CD names, and their biochemical properties and interacting partners were compiled primarily from several recent reviews. The information on experimentally determined structures of receptors or ligands shown in red is extracted from the Protein structure data bank (PDB) [10] in December 2014. Some related proteins of interest without CD names are at the end of the Table.


Columns are divided into three groups. The columns A-H concerning the NK-cell receptor, J-R concerning the supposed external ligands, and S-U devoted explicitly to function and morphology of the ligand-receptor complex under interest.


The Table is hopefully self-explaining. E.g. the column H (“Expression confirmed in”) contains the observed appearance of the receptor on different cell types. As an example, the m-CD30 is expressed only if NK-cells are activated and its interaction with CD156 may lead to proliferation of lymphocytes and apoptosis, by also to tolerance under specific conditions. It is evident that the tabulation requires extensive use of abbreviations. They are in consistency with those used in literature when it was possible. The detailed list of the abbreviations used in Table is alphabetically sorted by the end.


The related proteins from different species are resolved by a prefix (e.g. h-human, m-mouse) and are sorted on rows nearby (columns A,J). The table lists namely human and mouse receptors. Information on others species are here accidental and very sparse. The rows with human receptors have white background. The non-human receptors are marked by grey background. 


Interacting partners. The cellular receptor can have a number of interacting partners (listed in column G). Some of them have their principle role in natural processes in organisms, some have no evident function in organisms, some can have adverse function and other can be prepared on purpose artificially as a reaction of organisms to antigen (antibodies). Due to the high throughput methods for testing pairs of protein binding partners, the number of known interacting partners of receptors is continuously growing. Thus, in spite of a large number of the listed ligands, the Table is far to completeness.  The information on ligands in this Table is based on few recent reviews and the data extracted from the PDB. No global search of data scattered in individual journals, neither systematic search of ligands deposited in the PDB /10/ were done. The columns “Molecular morphology” are planned to explain the domain structure, complexation with intra and extracellular ligands and the observed multimerization of receptors, or ligands, or complexes.


The structures solved in our laboratory are highlighted by rose background. They include:  (a) the structures of NK-cell receptors (e.g. NKRP1A, NKRP1F, CD69) [4,5,6], (b) the structures of the protein molecules interacting with NK cell receptors (e.g. Clr-g, LLT1) [1,2,3], (c) studies of Fc fragment of IgG’s  interactions with cellular receptors [7,8], self-aggregation and formation of immuno-complexes via Fc fragment interactions [7], (d) the role of glycosylation on protein stability [8]. The structures of NK-cell related molecules determined worldwide are denoted yellow-green background.


The presented table of the structure data on NK-cell receptors and their ligands compiles a large volume of data from several available recent reviews. The data are accepted as they stated in the literature and no guaranty on correctness and accuracy is possible. The Table should be taken as a guide for the first orientation only. All facts should be verified elsewhere. The Table is updated occasionally by a staff involved in some special areas only and thus, it doesn’t cover the field completely. Therefore, it is open to changes suggested by external specialists. A current version of Table is available on the request from the first author (


The study was supported by ERDF BIOCEV CZ.1.05/1.1.00/02.0109, CSF 15-15181S,  P302/11/0855, MSMT  EE2.3.30.0029, LG14009, and GA FJFI SGS13/219/OHK4/3T/14.


1.         Skálová, T. et al (2015) Acta Crystallogr., D71, in press.

2.         Bláha, J. et al (2015) Protein Expression and Purification, 109, 7-13.

3.         Skálová, T. et al (2012) Journal of Immunology, 189, 10, 4881-4889.     

4.         Kolenko, P. et al (2011) Journal of Structural Biology, 175, 434-441.     

5.         Kolenko, P. et al (2011)  Acta Crystallogr.  F 67, 1519-1523.                     

6.         Kolenko, P. et al (2009)  Acta Crystallogr.  F 65, 1258-1260.                     

7.         Kolenko, P. et al (2009)  Immunology 126, 378-385.                                    

8.         Kolenko, P. et al (2008)  Coll.Czech.Chem.Soc. 73, 608-615.                      

9.         Rosen, D.B. et al (2008) Journal of Immunology, 6508-6517                     

10.       Berman, H.M. (2008) Acta Crystallogr. A64, 88-95.                                       

11.       Poster Human and Mouse CD molecules. (2014) Biolegend, California, version 04-0027-00.


12.       Exbio Praha, a.s. (2014),