title: Structural insights into the transmembrane domains of human copper transporter 1.
abstract: The human copper transporter 1 (hCtr1) mediates cellular uptake of copper and Pt-based chemotherapeutic anticancer drugs. In this paper, we determined the three-dimensional structure and oligomerization of the transmembrane domains (TMDs) of hCtr1 in 40% HFIP aqueous solution by using solution-state NMR spectroscopy. We firstly revealed that TMD1 forms an α-helical structure from Gly67 to Glu84 and is dimerized by close packing of its C-terminal helix; TMD2 forms an α-helical structure from Leu134 to Thr155 and is self-associated as a trimer by the hydrophobic contact of TMD2 monomers; TMD3 adopts a discontinuous helix structure, known as 'α-helix-coiled segment-α-helix', and is dimerized by the interaction between the N-terminal helices. The motif GxxxG in TMD3 is not fully involved in the helix, but partially unstructured as a linker between helices. The flexible linker of TMD3 may serve as a gating adapter to mediate pore on and off switch. The differences in the structure and aggregation of the TMD peptides may be related to their different roles in the channel formation and transport function.
authors.affiliation: State Key Laboratory of Supramolecular Structure and Materials, Jilin University, 2699 Qianjin Avenue, Changchun 130012, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Yang
authors.forename: Zhaowei
authors.initials: Z
authors.lastname: Huang
authors.forename: Fei
authors.initials: F
authors.lastname: Li
mesh_terms: D000595:Amino Acid Sequence; D027682:Cation Transport Proteins / Q000737:chemistry* / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism*; D000079923:Copper Transporter 1; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D017434:Protein Structure, Tertiary
chemical_list: D027682:Cation Transport Proteins; D000079923:Copper Transporter 1; C490079:SLC31A1 protein, human