TCB Publications - Abstract
Morten Ø. Jensen, Emad Tajkhorshid, and Klaus Schulten. The mechanism of glycerol conduction in aquaglyceroporins. Structure, 9:1083-1093, 2001.
Results: Molecular dynamics simulations of GlpF reveal spontaneous glycerol and water conduction driven, on a ns time scale, by thermal fluctuations. The bi-directional conduction, guided and facilitated by the secondary structure, is characterized by breakage and formation of hydrogen bonds for which water and glycerol compete. The conduction involves only very minor changes in the protein structure. Cooperativity between the GlpF monomers during conduction is not evident. The two conserved NPA motifs are strictly linked together by several stable hydrogen bonds. The two asparagine side chains of these motifs form hydrogen bonds with the substrates passing the channel in single file.
Conclusion: A complete conduction of glycerol through the E. coli glycerol facilitator, GlpF, was deduced from molecular dynamics simulations, and key residues facilitating the conduction were identified. The non-helical secondary structure of the two segments of the channel, formed by residues 64-66 and residues 199-201 exposes carbonyl oxygen atoms towards the channel interior, establishing a curve-linear conduction pathway. The conformational stability of the NPA motifs in GlpF is important in the conduction and critical for selectivity. Water and glycerol compete, in a random manner for hydrogen bonding sites in the protein, and their translocations, in single file, are correlated within each monomer. The protein structure is found remarkably stable, and no correlated conformational changes between monomers occurred. Regarding the highly conserved structure in the aquaporin family, the concluded mechanistic details apply to the whole family.
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