Molecular architecture and the structural basis for anion interaction in prestin and SLC26 transporters.
Prestin (SLC26A5) is a member of the SLC26/SulP anion transporter family. Its unique quasi-piezoelectric mechanical activity generates fast cellular motility of cochlear outer hair cells, a key process underlying active amplification in the mammalian ear. Despite its established physiological role, it is essentially unknown how prestin can generate mechanical force, since structural information on SLC26/SulP proteins is lacking. Here we derive a structural model of prestin and related transporters by combining homology modelling, MD simulations and cysteine accessibility scanning. Prestin's transmembrane core region is organized in a 7+7 inverted repeat architecture. The model suggests a central cavity as the substrate-binding site located midway of the anion permeation pathway, which is supported by experimental solute accessibility and mutational analysis. Anion binding to this site also controls the electromotile activity of prestin. The combined structural and functional data provide a framework for understanding electromotility and anion transport by SLC26 transporters.
1] Department of Neurophysiology, Institute of Physiology and Pathophysiology, Philipps University, 35037 Marburg, Germany [2].
Dmitry
D
Gorbunov
1] Department of Chemical Sciences, University of Padua, via Marzolo 1, Padova 35131, Italy [2].
Mattia
M
Sturlese
Department of Neurophysiology, Institute of Physiology and Pathophysiology, Philipps University, 35037 Marburg, Germany.
Florian
F
Nies
Department of Neurophysiology, Institute of Physiology and Pathophysiology, Philipps University, 35037 Marburg, Germany.
Murielle
M
Kluge
Department of Chemical Sciences, University of Padua, via Marzolo 1, Padova 35131, Italy.
Massimo
M
Bellanda
1] Department of Chemical Sciences, University of Padua, via Marzolo 1, Padova 35131, Italy [2] Venetian Institute for Molecular Medicine (VIMM), via Orus 2, Padova 35129, Italy.
Roberto
R
Battistutta
Department of Neurophysiology, Institute of Physiology and Pathophysiology, Philipps University, 35037 Marburg, Germany.
Dominik
D
Oliver
D000818:Animals; D027321:Anion Transport Proteins / Q000378:metabolism* / Q000502:physiology; D017920:Antiporters / Q000378:metabolism / Q000502:physiology; D002645:Chickens; D004330:Drosophila; D029721:Drosophila Proteins / Q000378:metabolism / Q000502:physiology; D029968:Escherichia coli Proteins / Q000378:metabolism; D018072:Hair Cells, Auditory, Outer / Q000378:metabolism* / Q000502:physiology; D026901:Membrane Transport Proteins / Q000378:metabolism; D051379:Mice; D008961:Models, Structural; D062105:Molecular Docking Simulation; D020409:Molecular Motor Proteins / Q000378:metabolism* / Q000502:physiology; D051381:Rats; D000076988:Sulfate Transporters; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000378:metabolism / Q000502:physiology
D027321:Anion Transport Proteins; D017920:Antiporters; D029721:Drosophila Proteins; D029968:Escherichia coli Proteins; D026901:Membrane Transport Proteins; D020409:Molecular Motor Proteins; C498720:Pres protein, mouse; C409207:Slc26a5 protein, rat; C466900:Slc26a6 protein, mouse; D000076988:Sulfate Transporters; C093118:UraA protein, E coli; D029961:Zebrafish Proteins; C000600831:prestin protein, Drosophila; C521130:slc26a5 protein, zebrafish