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. Author manuscript; available in PMC: 2012 May 10.
Published in final edited form as: Structure. 2011 May 11;19(5):733–747. doi: 10.1016/j.str.2011.02.009

Figure 8. Conserved Features of Apo Semi-Open EF-Hand Domains and Model for CaM:NaV1.2 Binding to Recognition Motifs.

Figure 8

A: Structural comparison of apo CaM76-148 (red):Nav1.2IQp (green rod) complex (2KXW) with the C-domains of apo CaM and apo CaM-like proteins (gray) bound to canonical IQ motifs (2IX7, 1M45, 1M46, 1ND2, and 3JVT). I and Q residues of all IQ motifs are sticks; Cα of residue 113 of CaM is a red sphere. B: Structural comparison of apo CaM76-148 (red):Nav1.2IQp (green rod) complex with the apo C-domain of (Ca2+)2-CaM1-148 (orange) bound to SKp (cyan). I1912 and Q1913 (Nav1.2IQp) and L428 and N426 (SKp) are ball-and-stick; CaM residue 113 shown as red or orange sphere. Sequences of Nav1.2IQp and SKp are aligned structurally based on the hydrophobic interaction of I1912 and L428 and carboxamide-containing Q1913 and N426. C: Two alternative polarities for peptides binding to the C-domain of CaM; NF-GC depicts the N-terminus (blue) closest to helix F (red), while CF-GN depicts the C-terminus (magenta) closest to helix F and farthest from helix G (orange). D: Relative positions of the hydrophobic (cyan spheres) and carboxamide (green spheres) residues. The blue-to-magenta color gradient indicates NF-GC polarity. E: Proposed model of CaM1-148 interacting with Nav1.2. The IQ motif interacts solely with the semi-open C-domain of CaM. The N-domain is in a closed conformation that may interact with an unidentified site X elsewhere on Nav1.2. Under Ca2+-saturating conditions, the C-domain remains bound to Nav1.2IQp; the open N-domain may bind to site Y (potentially distinct from site X). Supported by Figure S6.