title: Structure and metal ion binding of the first transmembrane domain of DMT1.
abstract: DMT1 is an integral membrane protein with 12 putative transmembrane domains. As a divalent metal ion transporter, it plays an important role in metal ion homeostasis from bacteria to human. Loss-function mutations at the conserved motif DPGN located within the first transmembrane domain (TMD1) of DMT1 indicate the significance of TMD1 in the biological function of the protein. In the present work, we study the structure, topology and metal ion binding of DMT1-TMD1 peptide by nuclear magnetic resonance using sodium dodecyl sulfate and dodecylphosphocholine micelles as membrane mimics. We find that the peptide forms an α-helix-extended segment-α-helix configuration in which the motif DPGN locates at the central flexible region. The N-terminal part of the peptide is deeply embedded in micelles, while the motif section and the C-terminal part are close to the surface of micelles. The peptide can bind to Mn2+ and Co2+ ions by the side chains of the negatively charged residues in the motif section and the C-terminal part of TMD1. The crucial role of the central flexible region and the C-terminal part of TMD1 in metal ion capture is confirmed by the binding of the N-terminal part truncated TMD1 to metal ions.
authors.affiliation: State Key Laboratory of Supramolecular Structure and Materials, Jilin University, Changchun, People's Republic of China.
authors.forename: Dan
authors.initials: D
authors.lastname: Wang
authors.forename: Yuande
authors.initials: Y
authors.lastname: Song
authors.forename: Jiantao
authors.initials: J
authors.lastname: Li
authors.forename: Chunyu
authors.initials: C
authors.lastname: Wang
authors.forename: Fei
authors.initials: F
authors.lastname: Li
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D027682:Cation Transport Proteins / Q000737:chemistry* / Q000378:metabolism; D003035:Cobalt / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D017136:Ion Transport; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008345:Manganese / Q000737:chemistry / Q000378:metabolism; D008670:Metals / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010767:Phosphorylcholine / Q000031:analogs & derivatives / Q000737:chemistry; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012967:Sodium Dodecyl Sulfate / Q000737:chemistry; D000099236:Solute Carrier Family 11, Member 2
chemical_list: D027682:Cation Transport Proteins; D003035:Cobalt; D008051:Lipid Bilayers; D008345:Manganese; D008670:Metals; D010767:Phosphorylcholine; D012967:Sodium Dodecyl Sulfate; D000099236:Solute Carrier Family 11, Member 2; C028810:dodecylphosphocholine