Crystal structure of human natural killer cell receptor NKp30 in complex with its tumor ligand B7-H6

T. Skálová1, O. Skořepa2, B. Kalousková2, J. Bláha2, C. Abreu2, J. Dohnálek1, O. Vaněk2

1 Institute of Biotechnology of the Czech Academy of Sciences, v.v.i., Průmyslová 595, 252 50, Vestec, Czech Republic, 2 Department of Biochemistry, Faculty of Science, Charles University Prague, Hlavova 8, 128 40 Praha, Czech Republic

NKp30 is an activating receptor on the surface of human natural killer (NK) cells. Its crystal structure is known since 2011, published and deposited by Joyce et al. [1] with PDB code 3NOI. B7-H6 is an activating immunoligand expressed by some tumor cells. Crystal structure of its complex with NKp30 has been published and deposited by Li et al. [2], PDB code 3PV6.


Here we present a new crystal structure of NKp30:B7-H6 at resolution 3.1 Å. While NKp30 in previous studies originated from bacterial productions, this is the first structure of the complex where both components come from eukaryotic cell lines. Both proteins are homogenously glycosylated and were produced in HEK293S GnTI- cells. For the structural study, NKp30 was used with complete glycosylation, while B7-H6 was deglycosylated after the first GlcNAc for better crystallization.


The new structure showed the same NKp30:B7-H6 interaction interface as observed by Li et al. (3PV6). Similarly as in the structure of Joyce et al. (3NOI), NKp30 form dimers; However, the dimers of glycosylated NKp30 are different (the glycan presence hinders the formation of the dimers observed in PDB 3NOI), and according to the PISA server validation, the new dimers are more likely biologically relevant. Furthermore, the asymmetric unit of the new crystal structure contains a dimer of NKp30 placed among two B7-H6 molecules (contacts of chains A-C and B-Dsymm). This arrangement may indicate possibility of binding of the NKp30 dimer between two B7-H6 ligands even during the contact of the NK cell and the tumor cell.


The structure has been deposited in the Protein Data Bank under code 6YJP and published [3].


[1]        Joyce, M.G., Tran, P., Zhuravleva, M.A., Jaw, J., Colonna, M., Sun, P.D. (2011) Proc. Natl. Acad. Sci. USA 108, 6223–6228.

[2]        Li, Y., Wang, Q., Mariuzza, R.A. (2011). J. Exp. Med. 208, 703–714.

[3]        Skořepa, O., Pazicky, S., Kalousková, B., Bláha, J., Abreu, C., Ječmen, T., Rosůlek, M., Fish, A., Sedivy, A., Harlos, K., Dohnálek, J., Skálová, T., Vaněk, O. (2020). Cancers 12, 1998.


This research was funded by Czech Science Foundation (18-10687S), MEYS of the Czech Republic (LTC17065, CZ.02.1.01/0.0/0.0/16_013/0001776), BIOCEV (ERDF CZ.1.05/1.1.00/02.0109), and Charles University (GAUK 927916, SVV 260427/2020). CIISB research infrastructure project LM2015043, funded by MEYS CR, is gratefully acknowledged for the financial support of experiments at the CMS. The authors also acknowledge the support and the use of Instruct-ERIC resources (PID: 1314) and iNEXT (PID: 2322) infrastructures. The Wellcome Centre for Human Genetics is supported by Wellcome Trust grant 203141/Z/16/Z. O.S. and O.V. received short-term scientific mission support from COST Action CA15126.