ArticleProtein science : a publication of the Protein Society2007
Human embryonic, fetal, and adult hemoglobins have different subunit interface strengths. Correlation with lifespan in the red cell.
Article in Protein science : a publication of the Protein Society, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 49 citations in OpenAlex.
- Reactivation of the embryonic ζ-globin gene ameliorates severe forms of α-thalassemia.Nature genetics · 2026Article
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- Hemoglobin alpha-like subunit mu is expressed during ontogeny and is elevated in alpha thalassemia.Blood red cells & iron · 2026Article
- Revisiting hemoglobin constant spring: molecular insights, pathophysiological mechanisms, and clinical perspectives.Orphanet journal of rare diseases · 2025Review
- Hypoxia favors tumor growth in colorectal cancer in an integrin αDβ1/hemoglobin δ-dependent manner.Life science alliance · 2025Article
- Exploring Novel Strategies to Alleviate Symptoms of β-Globinopathies: Examining the Potential Role of Embryonic ε-globin Induction.Transfusion medicine reviews · 2024Review
- Preparation and Utilization of a Highly Discriminative Absorbent Imprinted with Fetal Hemoglobin.Polymers · 2024Article
- Progresses in overcoming the limitations of in vitro erythropoiesis using human induced pluripotent stem cells.Stem cell research & therapy · 2024Review
- Initial Characterization of 3D Culture of Yolk Sac Tissue.Animals : an open access journal from MDPI · 2023Article
- Review
- Fetal and neonatal bilirubin metabolism.Frontiers in pediatrics · 2022Review
- BET inhibitors enhance embryonic and fetalHaematologica · 2021Article
- RNA chaperone activates Salmonella virulence program during infection.Nucleic acids research · 2021Article
- Detection of Common Deletional of α-Thalassemia 3.7 Kb from Metropolitan Region of Manaus, Amazonas, Brazil.Mediterranean journal of hematology and infectious diseases · 2021Article
- Recent Approaches for Manipulating Globin Gene Expression in Treating Hemoglobinopathies.Frontiers in genome editing · 2021Review
- Large-Scale Drug Screen Identifies FDA-Approved Drugs for Repurposing in Sickle-Cell Disease.Journal of clinical medicine · 2020Article
- Nano gel filtration reveals how fish hemoglobins release oxygen: The Root Effect.Analytical biochemistry · 2020Article
- Identifying genetic variants and pathways associated with extreme levels of fetal hemoglobin in sickle cell disease in Tanzania.BMC medical genetics · 2020Article
- Functional optical coherence tomography and photoacoustic microscopy imaging for zebrafish larvae.Biomedical optics express · 2020Article
- Gel filtration of dilute human embryonic hemoglobins reveals basis for their increased oxygen binding.Analytical biochemistry · 2017Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
The different types of naturally occurring, normal human hemoglobins vary in their tetramer-dimer subunit interface strengths (stabilities) by three orders of magnitude in the liganded (CO or oxy) state. The presence of embryonic zeta-subunits leads to an average 20-fold weakening of tetramer-dimer interfaces compared to corresponding hemoglobins containing adult alpha-subunits. The dimer-monomer interfaces of these hemoglobins differ by at least 500-fold in their strengths; such interfaces are weak if they contain zeta-subunits and exchange with added beta-subunits in the form of beta(4) (HbH) significantly faster than do those with alpha-subunits. Subunit exchange occurs at the level of the dimer, although tetramer formation reciprocally influences the amount of dimer available for exchange. Competition between subunit types occurs so that pairs of weak embryonic hemoglobins can exchange subunits to form the stronger fetal and adult hemoglobins. The dimer strengths increase in the order Hb Portland-2 (zeta(2)beta(2)) < Hb Portland-1 (zeta(2)gamma(2)) approximately equal Hb Gower-1 (zeta(2)epsilon(2)) < Hb Gower-2 (alpha(2)epsilon(2)) < HbF(1) < HbF (alpha(2)gamma(2)) < HbA(2) (alpha(2)delta(2)), i.e., from embryonic to fetal to adult types, representing maturation from weaker to stronger monomer-monomer subunit contacts. This increasing order recapitulates the developmental order in which globins are expressed (embryonic --> fetal --> adult), suggesting that the intrinsic binding properties of the subunits themselves regarding the strengths of interfaces they form with competing subunits play an important role in the dynamics of protein assemblies and networks.
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