title: The third and fourth transmembrane domains of Slc11a1: comparison of their structures and positioning in phospholipid model membranes.
abstract: Interactions of two peptides TM3 and TM4, corresponding to the third and fourth transmembrane domains of a divalent metal-ion transporter Slc11a1, respectively, with phospholipid model membranes, including zwitterionic dimyristoylphosphatidylcholine (DMPC) and anionic dimyristoylphosphatidylglycerol (DMPG), are studied in a wide range of peptide-to-lipid (P:L) ratios, and the secondary structures and positioning of the peptides in the lipid bilayers are analyzed, using differential scanning calorimetry (DSC), circular dichroism (CD), and fluorescence techniques. DSC and fluorescence results indicate that both peptides are inserted in the phospholipid bilayers. TM4 is buried in the bilayers more deeply and the insertion position is less affected by pH values, whereas TM3 is less deeply embedded and the position is remarkably shifted toward the direction of the bilayer surface with increasing pH value. The incorporation of TM4 in both lipids causes more perturbation to the packing of the hydrophobic chains of the lipids than TM3. Moreover, the perturbation of TM3 to the lipid packing is pH dependent, whereas the perturbation of TM4 is less pH dependent but with an unusually larger change in the enthalpy of the main transition at pH 5.5 than those at pH 4 and 7. CD data demonstrate that the main discrimination between the secondary structures of TM4 and TM3 is the alpha-helix content, more helicity for TM4 than TM3 in both lipids. The folding of the peptides is also affected by the composition of the phospholipids. Anionic lipid DMPG induces more alpha-helical folding than neutral lipid DMPC for both peptides.
authors.affiliation: State Key Laboratory of Supramolecular Structure and Materials, Jilin University, Changchun 130012, People's Republic of China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Qi
authors.forename: Lei
authors.initials: L
authors.lastname: Yang
authors.forename: Rong
authors.initials: R
authors.lastname: Xue
authors.forename: Yuande
authors.initials: Y
authors.lastname: Song
authors.forename: Shuo
authors.initials: S
authors.lastname: Wang
authors.forename: Fei
authors.initials: F
authors.lastname: Li
mesh_terms: D002152:Calorimetry, Differential Scanning; D027682:Cation Transport Proteins / Q000737:chemistry*; D002942:Circular Dichroism; D008051:Lipid Bilayers / Q000737:chemistry*; D008954:Models, Biological; D010743:Phospholipids / Q000737:chemistry*; D017433:Protein Structure, Secondary; D000099173:Natural Resistance-associated Macrophage Protein 1
chemical_list: D027682:Cation Transport Proteins; D008051:Lipid Bilayers; D010743:Phospholipids; D000099173:Natural Resistance-associated Macrophage Protein 1