Figure 4. The ternary complex between calmodulin (CaM) and two Na⁺/H⁺-exchanger (NHE1) H1s.

(a) Cartoon of the complex showing the two lobes of CaM in gray and the two NHE1 H1 helices in green. Ca²⁺ ions are shown in magenta. (b, c) Superimposition of the 10 lowest energy structures of the calculated ensemble aligned by (b) the CaM N-lobe with NHE1 H1 bound or (c) the CaM C-lobe with the second NHE1 H1 bound, showing mobility around the CaM linker. (d, e) Hydrophobic residues of NHE1 H1 forming contacts to CaM in the (d) N-lobe and (e) C-lobe, respectively. Electrostatic complementarity between Ca²⁺-CaM and NHE1-H1 in the (f) CaM N-lobe and the (g) CaM C-lobe shown by the surface potential of CaM and (h, i) for the two correspondingly bound H1 helices (PDB accession code 6zbi).

Figure 4—figure supplement 1. Comparison of the crystal structure (PDB: 2ygg) and the nuclear magnetic resonance (NMR) structure presented here (PDB: 6zbi).

(a) Crystal structure of the 1:1 Na⁺/H⁺-exchanger:calmodulin (NHE1:CaM) complex (PDB code: 2ygg) with the N-lobe bound to H2 and the backside of the C-lobe bound to H1 (PBD code: 6zbi). (b) Same as in (a) with a symmetry-related molecule of the crystal lattice included (red), showing that the hydrophobic cleft of the CaM C-lobe is occupied with H1 of this symmetry-related complex (H1_sym). (c) Side-by-side comparison of the structures of CaM N-lobe bound to H1 (NMR structure, left), CaM C-lobe bound to H1 (NMR structure, middle left), CaM C-lobe bound to H1_sym (crystal structure, middle right), and the CaM N-lobe bound to H2 (crystal structure, right). The three structures with H1 bound to the hydrophobic cleft of a CaM lobe are very similar to C^α-RMSDs of 2.3 Å (N-lobe + H1_NMR:C-lobe + H1_NMR), 1.8 Å (N-lobe + H1_NMR:C-lobe + H1_sym,X-ray), and 1.1 Å (C-lobe + H1_NMR:C-lobe + H1_sym,X-ray), respectively.