Navneet K. TyagiTheeraporn PuntheeranurakMobeen RajaAzad KumarBarbara WimmerIsabel NeundlingerHermann GruberPeter HinterdorferRolf K.H. KinneMax Planck Institut fur molekulare PhysiologieJohannes Kepler Universitat LinzHoward Hughes Medical InstituteMahidol UniversityUniversity of AlbertaNational Institute on Aging2018-05-032018-05-032011-01-01Biochimica et Biophysica Acta - Biomembranes. Vol.1808, No.1 (2011), 1-18000527362-s2.0-78649792808https://repository.li.mahidol.ac.th/handle/20.500.14594/11637Proteins 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, transp ort 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. © 2010 Elsevier B.V. All rights reserved.Mahidol UniversityBiochemistry, Genetics and Molecular BiologyReviewSCOPUS10.1016/j.bbamem.2010.07.028