Fig. 1

Alignment of PLCβ-interacting residues in Gα_q family and Gα_z. a Schematic view of Gα_q divided into helical (light blue) and GTPase (light green) domains with α-helices and β-strands represented by rectangles and ovals, respectively. Interacting domains of Gα_q with PLCβ are indicated by yellow boxes below the Gα_q sequence; the three bold segments indicate the relative positions of the three switch regions (Sw1 to Sw3 from left to right). Sequence alignment of PLCβ-interacting domains in the Gα_q family as compared to that of Gα_z; conserved (green) or divergent (red) PLCβ-interacting residues are interspersed by conserved residues which are not implicated in interaction with PLCβ (grey). Residues forming direct interactions with PLCβ3 as identified by Waldo et al. [13] are indicated by an asterisk. b Structural representation of Gα_q, Gα₁₄, and Gα_z alignments with switch regions (Sw1-3) and the α3 region. PLCβ3-interacting residues revealed in the sequence alignment are colored as indicated in A. Space filling models are showing interacting surfaces. Structural models of Gα₁₄ and Gα_z are generated based on Gα_q-PLCβ3 (PDB code: 3OHM) using SWISS-MODEL [65, 66]. Structure alignments are carried out with PyMOL (The PyMOL Molecular Graphics System, Version 1.3 Schrödinger, LLC). c Complex of Gα_q/Gα_z-PLCβ3. The Gα_q/Gα_z aligned model is represented as indicated in (B). PLCβ3 (yellow) is depicted as a cartoon ribbon, containing the helix-turn-helix segment (Hα1/Hα2), the N-terminal PH domain, four EF hands, the catalytic TIM barrel, and a C2 domain. The switch regions of Gα_q interact with PLCβ3 through an extended loop region between EF hands 3/4 and the region between the catalytic TIM barrel and C2 domain. The helix-turn-helix segment (Hα1/Hα2) at the C-terminus of PLCβ3 resides on the surface region formed by switch 2 and α3 of Gα_q. The α_N helix of Gα proteins and carboxy-terminal (CT) domain of PLCβ3 are not included in the structural models