Construction and validation of an atomic model for bacterial TSPO from electron microscopy density, evolutionary constraints, and biochemical and biophysical data.

Abstract : The 18kDa protein TSPO is a highly conserved transmembrane protein found in bacteria, yeast, animals and plants. TSPO is involved in a wide range of physiological functions, among which the transport of several molecules. The atomic structure of monomeric ligand-bound mouse TSPO in detergent has been published recently. A previously published low-resolution structure of Rhodobacter sphaeroides TSPO, obtained from tubular crystals with lipids and observed in cryo-electron microscopy, revealed an oligomeric structure without any ligand. We analyze this electron microscopy density in view of available biochemical and biophysical data, building a matching atomic model for the monomer and then the entire crystal. We compare its intra- and inter-molecular contacts with those predicted by amino acid covariation in TSPO proteins from evolutionary sequence analysis. The arrangement of the five transmembrane helices in a monomer of our model is different from that observed for the mouse TSPO. We analyze possible ligand binding sites for protoporphyrin, for the high-affinity ligand PK 11195, and for cholesterol in TSPO monomers and/or oligomers, and we discuss possible functional implications.
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https://hal.archives-ouvertes.fr/hal-01171268
Contributor : Isabelle Frapart <>
Submitted on : Friday, July 3, 2015 - 12:09:31 PM
Last modification on : Wednesday, October 9, 2019 - 2:57:48 PM

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Konrad Hinsen, Aurore Vaitinadapoule, Mariano A. Ostuni, Catherine Etchebest, Jean-Jacques Lacapere. Construction and validation of an atomic model for bacterial TSPO from electron microscopy density, evolutionary constraints, and biochemical and biophysical data.. Biochimica et Biophysica Acta:Biomembranes, Elsevier, 2015, 1848 (2), pp.568-580. ⟨10.1016/j.bbamem.2014.10.028⟩. ⟨hal-01171268⟩

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