Structural Model of the Bilitranslocase Transmembrane Domain Supported by NMR and FRET Data.
We present a 3D model of the four transmembrane (TM) helical regions of bilitranslocase (BTL), a structurally uncharacterized protein that transports organic anions across the cell membrane. The model was computed by considering helix-helix interactions as primary constraints, using Monte Carlo simulations. The interactions between the TM2 and TM3 segments have been confirmed by Förster resonance energy transfer (FRET) spectroscopy and nuclear magnetic resonance (NMR) spectroscopy, increasing our confidence in the model. Several insights into the BTL transport mechanism were obtained by analyzing the model. For example, the observed cis-trans Leu-Pro peptide bond isomerization in the TM3 fragment may indicate a key conformational change during anion transport by BTL. Our structural model of BTL may facilitate further studies, including drug discovery.
National Institute of Chemistry, Hajdrihova 19, Ljubljana, Slovenia.
Amrita
A
Roy Choudhury
Faculty of Chemistry, University of Gdańsk, Gdańsk, Poland.
Emilia
E
Sikorska
Institute for Structural and Medicinal Biochemistry, Center for Medical Biotechnology, University of Duisburg-Essen, Essen, Germany.
Johannes
J
van den Boom
Institute for Structural and Medicinal Biochemistry, Center for Medical Biotechnology, University of Duisburg-Essen, Essen, Germany.
Peter
P
Bayer
NanoBioMedical Center, Adam Mickiewicz University, Poznań, Poland.
Łukasz
Ł
Popenda
NanoBioMedical Center, Adam Mickiewicz University, Poznań, Poland; Faculty of Physics, Adam Mickiewicz University, Poznań, Poland.
Kosma
K
Szutkowski
NanoBioMedical Center, Adam Mickiewicz University, Poznań, Poland; Faculty of Physics, Adam Mickiewicz University, Poznań, Poland.
Stefan
S
Jurga
Department of Chemistry, University of Cambridge, Cambridge, United Kingdom; Department of Bioengineering and Therapeutic Sciences, Department of Pharmaceutical Chemistry, and California Institute for Quantitative Biosciences, University of California, San Francisco, California, United States of America.
Massimiliano
M
Bonomi
Department of Bioengineering and Therapeutic Sciences, Department of Pharmaceutical Chemistry, and California Institute for Quantitative Biosciences, University of California, San Francisco, California, United States of America.
Andrej
A
Sali
NanoBioMedical Center, Adam Mickiewicz University, Poznań, Poland; Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw, Poland.
Igor
I
Zhukov
Department of Life Sciences, University of Trieste, Trieste, Italy.
Sabina
S
Passamonti
National Institute of Chemistry, Hajdrihova 19, Ljubljana, Slovenia.
Marjana
M
Novič
D002462:Cell Membrane / Q000378:metabolism; D002570:Ceruloplasmin; D031541:Fluorescence Resonance Energy Transfer; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry*; D008823:Micelles; D008961:Models, Structural; D009010:Monte Carlo Method; D019906:Nuclear Magnetic Resonance, Biomolecular; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary
D008565:Membrane Proteins; D008823:Micelles; D002570:Ceruloplasmin; C033838:bilitranslocase