Interaction of natural killer cell receptor NKR-P1 with its ligand LLT1

Tereza Skálová¹, Jan Bláha², Jan Stránský¹, Tomáš Kovaľ¹, Jarmila Dušková¹, Yuguang Zhao³, Karl Harlos³, Ondřej Vaněk², Jan Dohnálek¹

¹Institute of Biotechnology, The Czech Academy of Sciences, v.v.i., Biocev, Průmyslová 595, 252 50 Vestec, Czech Republic,
²Department of Biochemistry, Faculty of Science, Charles University, Hlavova 8, 128 40 Prague, Czech Republic,
³Division of Structural Biology, The Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, OXFORD OX3 7BN, United Kingdom

t.skalova@gmail.com

Natural killer cells (NK cells) belong to innate immunity lymphocytes. They were discovered in 1970s and comprise 5-10% of lymphocytes circulating in blood. Their role in the immune system is to discover and kill cancer cells, stressed cells and cells infected by viruses. NK cells have a number of receptors on their surface, which are used for contact with other cells and for initiation of the cytotoxic response.

NKR-P1 is a C-type lectin like-receptor on surface of human natural killer cells and LLT1 is its binding partner belonging to the same structural family.

Recently, we have expressed, purified and solved four crystal structures of the extracellular part of LLT1 in monomeric, dimeric and hexameric form [1, 2]. In this contribution, we present three more structures characterizing this receptor-ligand binding pair: structures of the extracellular part of NKR-P1 in the fully glycosylated and deglycosylated form and a structure of the NKR-P1:LLT1 complex. Expression and purification of NKR-P1 was described by us recently as well [3].

All three crystal structures show NKR-P1 in a dimeric form with an unexpected dimerization mode. Unlike LLT1, which has the α2 helix in the dimerization interface, NKR-P1 dimer has the α1 helix in its dimerization interface. This different dimeric arrangement of both proteins enables spatial connection of NKR-P1 with LLT1 not only in a single molecular complex, but in a periodical chain of alternating receptor/ligand molecules. Such chain we really observe in the presented crystal structure.

1. Bláha, J. et al (2015).  Protein Expr. Purif. 109, 7-13. 

2. Skálová, T. et al (2015). Acta Cryst. D71, 578-591.

3. Bláha, J. et al (2017). Protein Expr. Purif. 140, 36-43.

This study was supported by BIOCEV (ERDF CZ.1.05/1.1.00/02.0109), CIISB4HEALTH (ERDF CZ.02.1.01/0.0/0.0/16_013/0001776), Czech Science Foundation (15-15181S and 18-10687S), MEYS of the Czech Republic (LTC17065 within the COST Action CA15126), Charles University (UNCE 204025/2012, GAUK 161216), and Instruct (R&D pilot scheme APPID 56 and 286).