Molecular dynamics study of the archaeal aquaporin AqpM

Abstract

BackgroundAquaporins are a large family of transmembrane channel proteins that are present throughout all domains of life and are implicated in human disorders. These channels, allow the passive but selective movement of water and other small neutral solutes across cell membranes. Aquaporins have been classified into two sub-families: i) strict aquaporins that only allow the passage of water and ii) the less selective aquaglyceroporins that transport water and other neutral solutes, such as glycerol, CO2 or urea. Recently, the identification and characterization of a number of archaeal and bacterial aquaporins suggested the existence of a third sub-family; one that is neither a strict aquaporin nor an aquaglyceroporin. The function and phylogeny of this third family is still a matter of debate.ResultsTwenty nanosecond molecular dynamics (MD) simulation of a fully hydrated tetramer of AqpM embedded in a lipid bilayer permitted predictions to be made of key biophysical parameters including: single channel osmotic permeability constant (pf), single channel diffusive permeability constant (pd), channel radius, potential water occupancy of the channel and water orientation inside the pore. These properties were compared with those of well characterized representatives of the two main aquaporin sub-families. Results show that changes in the amino acid composition of the aromatic/arginine region affect the size and polarity of the selectivity filter (SF) and could help explain the difference in water permeability between aquaporins. In addition, MD simulation results suggest that AqpM combines characteristics of strict aquaporins, such as the narrow SF and channel radius, with those of aquaglyceroporins, such as a more hydrophobic and less polar SF.ConclusionsMD simulations of AqpM extend previous evidence that this archaeal aquaporin exhibits hybrid features intermediate between the two known aquaporin sub-families, supporting the idea that it may constitute a member of a novel class of aquaporins.

Characterization of a Novel Water Pocket Inside the Human Cx26 Hemichannel Structure

“…In voltage-gated ion channels an Arg rich region in helix S4 is a key part of the voltage sensing mechanism (85)(86)(87). In aquaporins, a highly conserved Arg residue is a fundamental part of the selectivity filter (88)(89)(90) and different conformations of this residue inside the pore, affect the permeability of these channels (91)(92)(93). Moreover, the orientation of this Arg residue in aquaporins may response to external voltage, as described in MD simulations (94).…”

Comparative Genomics of the Genus Methanohalophilus, Including a Newly Isolated Strain From Kebrit Deep in the Red Sea

“…Marburg (Kozono et al, 2003). This archaeal type of aquaporin showed characteristics of both, aquaporin and aquaglyceroporin, the two existing classes of this protein family (Araya-Secchi et al, 2011). The presence of this gene implies a role for water channel mediated osmotically driven water flux in strain RSK that might aid cells to cope with sudden changes in salinity in their habitat.…”

Prokaryotic Aquaporins

“…Therefore, AqpM possesses a hybrid characteristic of the narrow channel radius of AqpZ and the more hydrophobic SF of GlpF. Accordingly, a molecular dynamics simulation suggested that AqpM has lower water permeability than E. coli AqpZ but greater than GlpF, whereas it has a significantly lesser glycerol permeability than GlpF [52]. Therefore, the hybrid features of the archaeal aquaporin AqpM between the two well-known aquaporin families indicate that it could represent a novel family of aquaporins.…”