HAH1 is a copper-binding protein with distinct amino acid residues mediating copper homeostasis and antioxidant defense.

The Journal of Biological Chemistry
I H HungJ D Gitlin

Abstract

HAH1 is a 68-amino acid protein originally identified as a human homologue of Atx1p, a multi-copy suppressor of oxidative injury in sod1 delta yeast. Molecular modeling of HAH1 predicts a protein structure of two alpha-helices overlaying a four-stranded antiparallel beta-sheet with a potential metal binding site involving two conserved cysteine residues. Consistent with this model, in vitro studies with recombinant HAH1 directly demonstrated binding of Cu(I), and site-directed mutagenesis identified these cysteine residues as copper ligands. Expression of wild type and mutant HAH1 in atx1 delta yeast revealed the essential role of these cysteine residues in copper trafficking to the secretory compartment in vivo, as expression of a Cys-12/Cys-15 double mutant abrogated copper incorporation into the multicopper oxidase Fet3p. In contrast, mutation of the highly conserved lysine residues in the carboxyl terminus of HAH1 had no effect on copper trafficking to the secretory pathway but eliminated the antioxidant function of HAH1 in sod1 delta yeast. Taken together, these data support the concept of a unique copper coordination environment in HAH1 that permits this protein to function as an intracellular copper chaperone mediating d...Continue Reading

References

Dec 1, 1977·Proceedings of the National Academy of Sciences of the United States of America·F SangerA R Coulson
Jan 1, 1990·Methods in Enzymology·F W StudierJ W Dubendorff
Oct 5, 1990·Journal of Molecular Biology·S F AltschulD J Lipman
Aug 1, 1984·Proceedings of the National Academy of Sciences of the United States of America·M P Yaffe, G Schatz
Jan 1, 1983·Journal of Bacteriology·H ItoA Kimura
Dec 5, 1995·Biochemistry·S Lutsenko, J H Kaplan
Mar 28, 1995·Proceedings of the National Academy of Sciences of the United States of America·D S YuanR D Klausner
Apr 25, 1995·Proceedings of the National Academy of Sciences of the United States of America·S J Lin, V C Culotta
Mar 20, 1995·Analytical Biochemistry·A J Brenner, E D Harris
Feb 1, 1995·Journal of Molecular Graphics·P Tufféry
Nov 30, 1993·Biochemical and Biophysical Research Communications·Y YamaguchiJ D Gitlin
Jan 1, 1993·Nature Genetics·J F MercerD Siemieniak
Jan 1, 1995·Annual Review of Nutrition·C D Vulpe, S Packman
Jun 14, 1996·The Journal of Biological Chemistry·D M GlerumA Tzagoloff
Nov 26, 1996·Proceedings of the National Academy of Sciences of the United States of America·Y YamaguchiJ D Gitlin
Apr 4, 1997·The Journal of Biological Chemistry·S J LinV C Culotta
Apr 4, 1997·The Journal of Biological Chemistry·L W KlompJ D Gitlin
Sep 20, 1997·The Journal of Biological Chemistry·V C CulottaJ D Gitlin
Nov 5, 1997·Science·R A PufahlT V O'Halloran
Apr 1, 1958·Archives of Biochemistry and Biophysics·G L ELLMAN

❮ Previous
Next ❯

Citations

Sep 17, 2013·The Journal of Membrane Biology·Adrian G Flores, Vinzenz M Unger
Jul 28, 2001·Progress in Neuro-psychopharmacology & Biological Psychiatry·J L Elliott
Jun 1, 2002·Current Opinion in Chemical Biology·Sergi Puig, Dennis J Thiele
Oct 15, 2009·Chemical Reviews·Amie K Boal, Amy C Rosenzweig
Nov 13, 2010·Metallomics : Integrated Biometal Science·Svetlana LutsenkoAnn L Hubbard
Aug 8, 2008·Proceedings of the National Academy of Sciences of the United States of America·Faiza HussainPernilla Wittung-Stafshede
Feb 5, 2008·The Journal of Biological Chemistry·Shinichi ItohTohru Fukai
Dec 20, 2012·Antioxidants & Redox Signaling·Yuta Hatori, Svetlana Lutsenko
Jun 6, 2006·Genome Research·Amardeep KaurNitin S Baliga
Jun 8, 2001·Annual Review of Biochemistry·D L Huffman, T V O'Halloran
Nov 12, 2002·Environmental Health Perspectives·Negah Fatemi, Bibudhendra Sarkar
Nov 11, 1999·Proceedings of the National Academy of Sciences of the United States of America·I HamzaJ D Gitlin
Jan 21, 2014·Progress in Neurobiology·Ivo F ScheiberRalf Dringen
Jan 17, 2007·Biometals : an International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine·Chloe Singleton, Nick E Le Brun
Feb 3, 2007·Biometals : an International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine·Mee Y Bartee, Svetlana Lutsenko
Aug 12, 2008·Journal of Molecular Biology·Agustina Rodriguez-GranilloPernilla Wittung-Stafshede
Sep 21, 2007·Biochimica Et Biophysica Acta·Faiza Hussain, Pernilla Wittung-Stafshede
Sep 28, 2015·Biochimie·Francesca Ronca, Antonio Raggi
Dec 22, 2005·The Plant Journal : for Cell and Molecular Biology·Nuria Andrés-ColásLola Peñarrubia
Jan 20, 2006·Pigment Cell Research·Ning Wang, Daniel N Hebert
Jun 23, 2010·Archives of Insect Biochemistry and Physiology·Charles DarkohBeatrice Clack
Feb 5, 2011·Mitochondrion·María Pilar Bayona-BafaluyJosé Antonio Enríquez
Jul 15, 1999·Structure·A C RosenzweigT V O'Halloran
Mar 16, 2017·IUBMB Life·Yuta HatoriReiko Akagi
Jan 8, 2004·The Journal of Biological Chemistry·Amy K WernimontAmy C Rosenzweig

❮ Previous
Next ❯

Related Concepts

Related Feeds

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.