ATP-induced Tetramerization and Cooperativity in Hemoglobin of Lower Vertebrates
Open accessAbstract
The importance of intraerythrocytic organic phosphates in the allosteric control of oxygen binding to vertebrate hemoglobin (Hb) is well recognized and is correlated with conformational changes of the tetramer. ATP is a major allosteric effector of snake Hb, since the absence of this nucleotide abolishes the Hb cooperativity. This effect may be related to the molecular weight of about 32,000 for this Hb, which is compatible with the dimeric form. ATP induces a pH-dependent tetramerization of deoxyHb that leads to the recovery of cooperativity. This phenomenon may be partially explained by two amino acid replacements in the beta chains (CD2 Glu-43 --> Thr and G3 Glu-101 --> Val), which result in the loss of two negative charges at the alpha1beta2 interface and favors the dissociation into dimers. The ATP-dependent dimer left arrow over right arrow tetramer may be physiologically important among ancient animal groups that have similar mutations and display variations in blood pH that are governed by these animals' metabolic state. The enormous loss of free energy of association that accompanies Hb oxygenation, and which is also observed at a much lower intensity in higher vertebrate Hbs, must be taken into consideration in allosteric models. We propose that the transition from a myoglobin-like protein to an allosteric one may be of evolutionary significance.
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Increased avidity through multimerisation is well known, but it remains less well characterised in the context of transcription factor biology.
“While increased avidity through multimerisation is well known (e.g. haemoglobin 69,70 ), it remains less well characterised in the context of TF biology 71 .”
From Tetramerisation governs SALL transcription factor function in development and disease (2025) · cites this paper as [69]
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BackgroundInfluentialTetramerisation governs SALL transcription factor function in development and disease
Giuliani, S., Chhatbar, K., Wear, M., Guy, J., Mathieson, T., Burdett, H., George, L., Alston, G., Spanos, C., McHugh, T., et al. (2025) · bioRxiv · doi:10.1101/2025.10.27.684836
- Authors
- Bonafe, C. F. S., Matsukuma, A. Y., & Matsuura, M. S. A.
- Affiliations
- Universidade Estadual de Campinas (UNICAMP) (BR)
- Corresponding author
- Matsuura, Maria S.A.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1999-01
- Volume
- 274
- Issue
- 3
- Pages
- 1196-1198
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2088940183
- Cited by
- 15
- References
- 28
- Citations by year
- 2025: 1 · 2019: 1 · 2018: 1 · 2016: 1 · 2015: 1
- FWCI
- 0.35
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hemoglobin structure and function
- Health Sciences › Medicine › Genetics › Hemoglobinopathies and Related Disorders
- Health Sciences › Medicine › Surgery › Biomedical and Chemical Research
- Keywords
- hemoglobin, ATP, allosteric cooperativity, tetramerization, lower vertebrates, organic phosphates, deoxyhemoglobin, blood pH, oxygen binding, free energy of association
- MeSH terms
- Adenosine Triphosphate, Animals, Female, Hemoglobins, Humans, Hydrogen-Ion Concentration, Male, Models, Chemical, Molecular Weight, Oxygen, Organophosphates, Protein Conformation, Snakes
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