Fig. 5: Structure of AE2 in the absence of PIP2.
From: Structural and functional insights into the lipid regulation of human anion exchanger 2
a, b Cryo-EM density map of AE2IF/REST state (AE2 with R932A/K1147A/H1148A mutations in the inward-facing conformation), viewed from the side (a) and the cytoplasmic side (b). The approximate position of the lipid bilayer is indicated by gray bars. The two AE2 protomers are colored in green and blue, respectively. c Structural comparison of the TMDs of AE2IF/REST and AE2IF/PIP2 aligned by the gate domain. Two PIP2 molecules and the TMD of AE2IF/PIP2 are colored in yellow, orange and gray, respectively. The two protomers of AE2IF/REST are colored in blue and green, respectively. d Structural comparison of one protomer of each of the AE2IF/PIP2 and AE2IF/REST states. The gate domain and core domain of AE2IF/REST are colored in blue and green, respectively. Two PIP2 molecules and the TMD of AE2IF/PIP2 are colored in yellow, orange and gray, respectively. Arrows indicate the displacements of the core domain from the AE2IF/PIP2 state to the AE2IF/REST state. e Structural comparison of the PIP2 binding site in the AE2IF/PIP2 and AE2IF/REST states. The Cα distance between I935 in the AE2IF/PIP2 and AE2IF/REST states are shown as a dashed line. The gate domain and core domain of AE2IF/REST are colored in blue and green, respectively. AE2IF/PIP2 is colored in gray. f Interface of the AE2IF/REST NTD and the core domain of the TMD. The loop connecting TM10 to TM11 is colored in green and the NTD is colored in pink. Residues within the interface are shown as sticks and interactions between residues are indicated by dashed lines. g Interface of AE2IF/REST NTD and gate domain of TMD of the other protomer. NTD is colored in pink and gate domain of the other protomer is colored in blue. Residues within the interface are shown as sticks and interactions between residues are indicated by dashed lines.
