Identification of a novel zinc-binding protein, C1orf123, as an interactor with a heavy metalassociated domain

Yoshiaki Furukawa, Carolyn Lim, Takehiko Tosha, Koki Yoshida, Tomoaki Hagai, Shuji Akiyama, Shoji Watanabe, Kenta Nakagome, Yoshitsugu Shiro

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Heavy metal-associated (HMA) domains bind metal ions at its Cys-x-x-Cys (CxxC) motif and constitute an intracellular network for trafficking of metal ions for utilization and detoxification. We thus expect that novel metalloproteins can be identified by screening proteins interacting with a HMA domain. In this study, we performed yeast two-hybrid screening of the human proteome and found an uncharacterized protein encoded as open reading frame 123 in chromosome 1 (C1orf123) that can interact specifically with the HMA domain of a copper chaperone for superoxide dismutase (CCSdI). Our X-ray structural analysis of C1orf123 further revealed that it binds a Zn 2+ ion in a tetrahedral coordination with four thiolate groups from two conserved CxxC motifs. For the interaction between C1orf123 and CCSdI, the CxxC motifs in both C1orf123 and CCSdI were required, implying metal-mediated interaction through the CxxC motifs. Notably, C1orf123 did not interact with several other HMA domains containing CxxC motifs, supporting high specificity in the interaction between C1orf123 and CCSdI. Based upon these results, we further discuss functional and structural significance of the interaction between C1orf123 and CCS.

元の言語English
記事番号e0204355
ジャーナルPloS one
13
発行部数9
DOI
出版物ステータスPublished - 2018 9

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Furukawa, Y., Lim, C., Tosha, T., Yoshida, K., Hagai, T., Akiyama, S., Watanabe, S., Nakagome, K., & Shiro, Y. (2018). Identification of a novel zinc-binding protein, C1orf123, as an interactor with a heavy metalassociated domain. PloS one, 13(9), [e0204355]. https://doi.org/10.1371/journal.pone.0204355