A Mets motif peptide found in copper transport proteins selectively binds Cu(I) with methionine-only coordination.

Journal Article

Mets motifs, which refer to methionine-rich sequences found in the high-affinity copper transporter Ctr1, also appear in other proteins involved in copper trafficking and homeostasis, including other Ctrs as well as Pco and Cop proteins isolated from copper-resistant bacteria. To understand the coordination chemistry utilized by these proteins, we studied the copper binding properties of a peptide labeled Mets7-PcoC with the sequence Met-Thr-Gly-Met-Lys-Gly-Met-Ser. By comparing this sequence to a series of mutants containing noncoordinating norleucine in place of methionine, we confirm that all three methionine residues are involved in a thioether-only binding site that is selective for Cu(I). Two independent methods, one based on mass spectrometry and one based on rate differences for the copper-catalyzed oxidation of ascorbic acid, provide an effective K(D) of approximately 2.5 microM at pH 4.5 for the 1:1 complex of Mets7-PcoC with Cu(I). These results establish that a relatively simple peptide containing an MX(2)MX(2)M motif is sufficient to bind Cu(I) with an affinity that corresponds well with its proposed biological function of extracellular copper acquisition.

Full Text

Duke Authors

Cited Authors

  • Jiang, J; Nadas, IA; Kim, MA; Franz, KJ

Published Date

  • December 26, 2005

Published In

Volume / Issue

  • 44 / 26

Start / End Page

  • 9787 - 9794

PubMed ID

  • 16363848

International Standard Serial Number (ISSN)

  • 0020-1669

Digital Object Identifier (DOI)

  • 10.1021/ic051180m

Language

  • eng

Conference Location

  • United States