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Structural insights into the transmembrane domains of human copper transporter 1
Author(s) -
Yang Lei,
Huang Zhaowei,
Li Fei
Publication year - 2012
Publication title -
journal of peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 66
eISSN - 1099-1387
pISSN - 1075-2617
DOI - 10.1002/psc.2415
Subject(s) - linker , helix (gastropod) , transmembrane domain , trimer , chemistry , copper , crystallography , biophysics , nuclear magnetic resonance spectroscopy , transmembrane protein , transporter , stereochemistry , membrane , biochemistry , dimer , biology , receptor , gene , organic chemistry , snail , computer science , operating system , ecology
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. Copyright © 2012 European Peptide Society and John Wiley & Sons, Ltd.