Our lab is interested in metal ion homeostasis in eukaryotes. Metal ions have many diverse roles in biology, and are cofactors in approximately one third of all proteins and one half of all enzymes. Although most proteins in healthy cells obtain their correct metal cofactor, it is largely unclear how they do so. If a nascent polypeptide is provided with a mix of divalent metal cations, it will bind ions preferentially according to the Irving Williams series (Mn2+ < Fe2+ < Co2+ < Cu2+ > Zn2+). As metals at the top of this series typically form more stable protein complexes than metals at the bottom of the series, this leads to an unsolved biological problem of how all metalloproteins obtain their correct cofactor. Aberrant metal ion levels can be detrimental to health; therefore an understanding of fundamental aspects of basic metal ion homeostasis can provide insight into human disease.
Corkins ME, May M, Ehrensberger KM, Hu YM, Liu YH, Bloor SD, Jenkins B, Runge KW, Bird AJ (2013) Zinc finger protein Loz1 is required for zinc-responsive regulation of gene expression in fission yeast. Proc Natl Acad Sci USA 103:8674-79.
Ehrensberger KE, Mason C, Corkins, ME, Anderson C, Dutrow N, Cairns B, Dalley B, Milash B, and Bird AJ (2013) Zinc-dependent regulation of the adh1 antisense transcript in fission yeast. J Biol Chem. 288:759-769.
Ehrensberger KE and Bird AJ (2011) Hammering out details: Regulating metal levels in eukaryotes. TIBS 36:524-31
Frey AG, Bird AJ, Blankman E, Evans-Galea M, Winge DR, and Eide DJ (2011) Zinc-regulated DNA Binding of the yeast Zap1 zinc-responsive activator. PLOS One 6:e22535
Wu CY, Roje S, Sandoval FJ, Bird AJ, Winge DR, and Eide DJ (2009) Repression of sulfate zinc assimilation is an adaptive response of yeast to the oxidative stress of deficiency. J Biol Chem 284:27544-56
Wu CY, Bird AJ, Chung LM, Newton MA, Winge DR and Eide DJ (2008) Differential control of Zap1-regulated genes in response to zinc deficiency in Saccharomyces cerevisiae. BMC Genomics 9:370-387
Khalimonchuk O, Bird AJ and Winge DR (2007) Evidence for a pro-oxidant intermediate in the assembly of cytochrome oxidase. J Biol Chem 282:17442-9
Bird AJ (2007) Metallosensors, the ups and downs of gene regulation. Adv Microb Physiol 53:232-57
Bird AJ, Gordon M, Eide DJ and Winge DR (2006) Repression of ADH1 and ADH3 gene expression during zinc deficiency by Zap1-induced intergenic RNA transcripts. EMBO J 25:5726-34.
Chang-Yi W, Bird AJ, Winge DR and Eide DJ (2006) Regulation of the yeast Tsa1 peroxiredoxin by Zap1 is an adaptive response to the oxidative stress of zinc deficiency. J Biol Chem 282:2184-95.
Bird AJ, Swierczek S, Qiao W, Eide DJ and Winge DR (2006) Zinc metalloregulation of the zinc finger pair domain. J Biol Chem 281:25326-35.
Qiao W, Mooney M, Bird AJ, Winge DR and Eide DJ (2006) Zinc binding to a regulatory zinc-sensing domain monitored in vivo by using FRET. Proc Natl Acad Sci USA 103:8674-79.
Keller G, Bird AJ and Winge DR (2005) Independent Metalloregulation of Ace1 and Mac1 in Saccharomyces cerevisiae. Eukaryot Cell 4:1863-71.
Herbig A, Bird AJ, McCall K, Mooney M, Chang-Yi W, Eide DJ and Winge DR (2005) Zap1 activation domain I and its role in controlling gene expression in response to cellular zinc status. Mol Microbiology 57:834-46.
Bird AJ, Blankman E, Stillman DJ, Eide DJ and Winge DR (2004) The Zap1 transcriptional activator also acts as a repressor by binding downstream of the TATA box in ZRT2. EMBO J 23:1123-1132.
Rutherford JC and AJ Bird (2004) Metal-responsive transcription factors that regulate iron, zinc and copper homeostasis in eukaryotic cells. Eukaryot Cell B:1-13.
Bird AJ, McCall K, Kramer M, Blankman E, Winge DR and Eide DJ (2003) Zinc fingers act as Zn2+ sensors for regulation of activation domain function in the yeast Zap1 transcriptional activator. EMBO J 22:1-10.
Evans-Galea M, Blankman E, Myszka D, Bird AJ, Eide DJ and Winge DR (2002) Two of the five zinc fingers in the Zn-regulated Zap1 transcription factor dominate site-specific DNA binding. Biochemistry 42:1053-1061.
Bird AJ, Zhao H, Luo H, Jenson LT, Srinivasan C, Evans-Galea M, Winge DR and Eide DJ (2000) A dual role for zinc fingers in both DNA binding and zinc sensing by the Zap1 transcriptional activator. EMBO J 19:1-10.
Bird AJ, Evans-Galea M, Blankman E, Zhao H, Luo H, Winge DR and Eide DJ (2000) Mapping the DNA binding domain of the Zap1 zinc-responsive transcriptional activator. J Biol Chem 275:16160-16166.
Bird AJ, Turner-Cavet JS, Lakey JH and Robinson NJ (1997) A carboxyl-terminal Cys2/His2-type zinc finger motif in DNA primase influences DNA content in Synechococcus PCC 7942. J Biol Chem 273:21246-21252.