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Intrinsic regulation of hemoglobin expression by variable subunit interface strengths
Author(s) -
Manning James M.,
Popowicz Anthony M.,
Padovan Julio C.,
Chait Brian T.,
Manning Lois R.
Publication year - 2012
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2011.08437.x
Subject(s) - protein subunit , microbiology and biotechnology , gene expression , transcription (linguistics) , gene , biophysics , biology , chemistry , acetylation , genetics , linguistics , philosophy
The expression of the six types of human Hb subunits over time is currently considered to be regulated mainly by transcription factors that bind to upstream control regions of the gene (the ‘extrinsic’ component of regulation). Here, we describe how subunit pairing and further assembly to tetramers in the liganded state is influenced by the affinity of subunits for one another (the ‘intrinsic’ component of regulation). The adult Hb dimers have the strongest subunit interfaces and the embryonic Hbs the weakest, with fetal Hbs being of intermediate strength, corresponding to the temporal order of their expression. These variable subunit binding strengths and the attenuating effects of acetylation contribute to the differences with which these Hb types form functional O 2 ‐binding tetramers consistent with gene switching.