Open AccessIdentification of a novel zinc-binding protein, C1orf123, as an interactor with a heavy metal-associated domain
Author(s) -
Yoshiaki Furukawa,
Carolyn Lim,
Takehiko Tosha,
Koki Yoshida,
Tomoaki Hagai,
Shuji Akiyama,
Shôji Watanabe,
Kenta Nakagome,
Yoshitsugu Shiro
Publication year - 2018
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0204355
Subject(s) - metalloprotein , interactor , biology , proteome , biochemistry , structural motif , open reading frame , chaperone (clinical) , protein–protein interaction , computational biology , peptide sequence , microbiology and biotechnology , gene , enzyme , medicine , pathology
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 (CCS dI ). 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 CCS dI , the CxxC motifs in both C1orf123 and CCS dI 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 CCS dI . Based upon these results, we further discuss functional and structural significance of the interaction between C1orf123 and CCS.