Slc11a1 is an integral membrane protein with 12 putative transmembrane domains and functions as a pH-coupled divalent metal cation transporter. In the present study, the structures of the peptides corresponding to the second and fifth transmembrane domains of Slc11a1 (from 88 to 109 for TMD2 and from 190 to 215 for TMD5) were determined in membrane-mimic environments by CD and NMR techniques. It was demonstrated that TMD2 and TMD5 form an α-helical structure in 30% 2,2,2-trifluoroethanol (TFE) and 40% hexafluoro-2-propanol (HFIP) aqueous solution, respectively. The α-helix of TMD5 displays a less space-occupied face consisting of the residues Ala194, Gly197, Thr201, Ala204 and Gly208. The α-helix is partially unfolded in the N-terminal region when Gly197 is substituted by Val. The unfolding of the helix in the N-terminal part and/or increase in volume at the less space-occupied face of the helix may exert an effect on the arrangement of TMD5 in membrane. Copyright © 2014 European Peptide Society and John Wiley & Sons, Ltd.
The second transmembrane domain TMD2 of Slc11a1 was revealed to adopt an α-helical structure in membrane-mimic environment. The fifth transmembrane domain TMD5 of Slc11a1 was found to form an α-helix with a less space-occupied face, and the α-helix is partially unfolded in the N-terminal region when Gly197 is substituted by Val.