Fig. 7 | Nature Communications

Fig. 7

From: Identification of rare sequence variation underlying heritable pulmonary arterial hypertension

Fig. 7

Structural analysis of AQP1 mutations. a Multiple sequence alignment of human AQP1 with seven other mammals. The bovine AQP1 has the high resolution (2.2 Å) published structure. Mutations identified in PAH cases are highly conserved and highlighted in yellow. b Crystal structure of bovine AQP1 (PDB: 1j4n)22. Left: side view; right: top view from the extracellular direction. AQP1 is shown as a semi-transparent cartoon and five water molecules in the water channel are shown as red spheres. Key residues lining the water channels are represented with stick structures. c Magnified view of the water channel, with H-bonds connected to water molecules in the channel highlighted. Two asparagine-proline-alanine (NPA) motifs, essential for the water transporting function of AQP1, are shown in magenta. Conserved His180 that constricts the water channel is shown in yellow. Mutations found in PAH cases, Arg195Trp and Val176Glu, are labelled and shown as orange stick structures. Arg195 and His180 are highly conserved in the known water channels and are strong indicators of water channel specificity. Arg195Trp and Val176Glu mutations are predicted to disrupt the conformation of this conserved water channel

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