title: A biophysical glance at the outer surface of the membrane transporter SGLT1.
abstract: Proteins mediating the transport of solutes across the cell membrane control the intracellular conditions in which life can occur. Because of the particular arrangement of spanning a lipid bilayer and the many conformations required for their function, transport proteins pose significant obstacles for the investigation of their structure-function relation. Crystallographic studies, if available, define the transmembrane segments in a "frozen" state and do not provide information on the dynamics of the extramembranous loops, which are similarly evolutionary conserved and thus as functionally important as the other parts of the protein. The current review presents biophysical methods that can shed light on the dynamics of transporters in the membrane. The techniques that are presented in some detail are single-molecule recognition atomic force microscopy and tryptophan scanning, which can report on the positioning of the loops and on conformational changes at the outer surface. Studies on a variety of symporters are discussed, which use gradients of sodium or protons as energy source to translocate (mainly organic) solutes against their concentration gradients into or out of the cells. Primarily, investigations of the sodium-glucose cotransporter SGLT1 are used as examples for this biophysical approach to understand transporter function.
authors.affiliation: Max Planck Institute of Molecular Physiology, Otto-Hahn-Strasse 11, D-44227 Dortmund, Germany.
authors.forename: Navneet K
authors.initials: NK
authors.lastname: Tyagi
authors.forename: Theeraporn
authors.initials: T
authors.lastname: Puntheeranurak
authors.forename: Mobeen
authors.initials: M
authors.lastname: Raja
authors.forename: Azad
authors.initials: A
authors.lastname: Kumar
authors.forename: Barbara
authors.initials: B
authors.lastname: Wimmer
authors.forename: Isabel
authors.initials: I
authors.lastname: Neundlinger
authors.forename: Hermann
authors.initials: H
authors.lastname: Gruber
authors.forename: Peter
authors.initials: P
authors.lastname: Hinterdorfer
authors.forename: Rolf K H
authors.initials: RK
authors.lastname: Kinne
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001703:Biophysics / Q000379:methods*; D002462:Cell Membrane / Q000378:metabolism*; D018360:Crystallography, X-Ray / Q000379:methods; D006801:Humans; D008024:Ligands; D018625:Microscopy, Atomic Force / Q000379:methods; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D051269:Sodium-Glucose Transporter 1 / Q000235:genetics* / Q000502:physiology*; D014364:Tryptophan / Q000737:chemistry
chemical_list: D008024:Ligands; C495674:SLC5A1 protein, human; D051269:Sodium-Glucose Transporter 1; D014364:Tryptophan