Fig. 8: Organization of the NKR-P1:LLT1 complexes on the cell surface.

a Representation of four adjacent asymmetric units within the NKR-P1:LLT1 complex crystal, excluding the additional unrelated NKR-P1 dimer. The NKR-P1 (blue and cyan) and LLT1 (green and lemon) dimers alternate in primary (cyan and green) and secondary (blue and lemon) interactions, forming a chain-like structure. The schematic depiction of this arrangement is shown in the inset with the same color code. The black and white triangles represent N-termini positions, pointing behind and in front of the display plane, respectively. b Depiction of the hypothetical arrangement of the chain-like structure upon contact of an NK cell (bottom, blue) with a target cell (top, green) showing the crystal structure of two NKR-P1 dimers (cyan and blue) interacting with two LLT1 dimers (green and lemon) in the primary (cyan and green) and secondary (blue and lemon) modes. The first three N-terminal residues in the structures are highlighted in red. The flexible stalk regions connecting the N-termini and cell membranes are represented as speckled lines of the corresponding color-coding. The view on the right-hand side is clipped for clarity at the plane indicated on the left-hand side view. c Schematic depiction of NKR-P1 extracellular domain dynamics and possible ligand binding arrangements. NKR-P1 is expressed as a disulfide-linked homodimer; however, its CTLDs may undergo conformation change similar to monomer-dimer equilibrium. Such putative equilibrium would be shifted towards monomeric species for the wild-type protein and its I168T allelic variant⁵¹. At the same time, a dimeric arrangement corresponding to the non-covalent dimer observed in the herein described crystal structures would be promoted for the S159A variant (left-hand side). Such NKR-P1 dimer could then interact with the cognate LLT1 ligand (itself being expressed as a disulfide-linked homodimer as well and forming stable non-covalent dimers with its CTLDs) in the previously suggested standard model of NK cell receptor – CTL ligand interaction (middle) or alternate with the dimeric ligand in the proposed chain-like arrangement based on NKR-P1:LLT1 complex crystal structure (right-hand side).