Dimer-tetramer transition in hemoglobins from Liophis miliaris—I. Effect of organic polyphosphates

Matsuura, Maria Sumiko Arita; Ogo, Satie Hatsushika; Focesi, Aldo

doi:10.1016/0300-9629(87)90624-4

Cited by 30 publications

(9 citation statements)

References 12 publications

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“…1). Stripped snake Hb showed a high affinity for O 2 and no allosterism, in accordance with a molecular mass compatible with the dimeric form (3,10,15). In the presence of organic phosphates, the molecule became cooperative (n H ϭ 2) with a low O 2 affinity at a pH up to 7.4.…”

Section: Resultsmentioning

confidence: 84%

ATP-induced Tetramerization and Cooperativity in Hemoglobin of Lower Vertebrates

Bonafé

Matsukuma

Matsuura

1999

Journal of Biological Chemistry

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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 ␤ chains (CD2 Glu-43 3 Thr and G3 Glu-101 3 Val), which result in the loss of two negative charges at the ␣ 1 ␤ 2 interface and favors the dissociation into dimers. The ATP-dependent dimer 7 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.In vertebrates, hemoglobin (Hb) exists as a tetramer in its intraerythrocytic environment, and it is this form that is involved in the classic structural change from a low to a high O 2 affinity molecule in the presence of increasing O 2 concentrations. This phenomenon, known as cooperativity, is reflected in the sigmoidal shape of the O 2 saturation curve.Protons and organic phosphate are important in the physiological transport of O 2 in most vertebrate groups, since they stabilize the low affinity form of Hb (1, 2).Previous studies have demonstrated an oxygen-induced dissociation of snake Hb at physiological pH and Hb concentration, as well as in the presence of high levels of organic phosphate (3). The structural basis of this phenomenon is the replacement of amino acid residues ␤-CD2-43 and ␤-G3-101 at the ␣ 1 ␤ 2 interface which is responsible for tetramer stabilization. These key residues, normally both glutamic acid, are replaced by threonine and valine, respectively, in snake Hb (4). This loss of negative charges would disturb the interface contact, leading to a pronounced tendency of Hb to dissociate into dimers. Since these residues are also replaced in most hemoglobins from ectothermic animals (5-9), this suggests that a dissociation of Hb occurs during oxygenation. The physiological role of such Hb dissociation is considered in the present investigation. EXPERIMENTAL PROCEDURESHemoglobin Preparation-Adult snakes of both sexes weighing 200 -400 g were obtained from the Instituto Butantã (Sã o Paulo) and were kept in the laboratory until bleeding. The hemolysate was prepared as described by Rossi-Fanelli and Antonini (10) and was freed of salts and small organic molecules by passage thro...

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Section: Resultsmentioning

confidence: 84%

ATP-induced Tetramerization and Cooperativity in Hemoglobin of Lower Vertebrates

Bonafé

Matsukuma

Matsuura

1999

Journal of Biological Chemistry

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“…The dissociation of the large complexes of oxygenated P. palpebrosus Hb into smaller molecules upon deoxygenation contrasts starkly with the deoxygenation-linked self-association encountered in Hbs of other ectothermic vertebrates (65), including hagfish and lampreys (monomer to dimer) (14,26), snakes (dimer to tetramer) (29,54), frogs Rana esculenta and R. temporaria (tetramer to dimer of tetramers) (5,23), and bullfrog R. catesbiana (tetramer to heterotrimer of tetramers) (83).…”

Section: Polymerization and Its Effect On Hb-o 2 Bindingmentioning

confidence: 96%

Lack of conventional oxygen-linked proton and anion binding sites does not impair allosteric regulation of oxygen binding in dwarf caiman hemoglobin

Weber

Fago

Malte

et al. 2013

American Journal of Physiology-Regulatory, Integrative and Comp

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In contrast to other vertebrate hemoglobins (Hbs) whose high intrinsic O2 affinities are reduced by red cell allosteric effectors (mainly protons, CO2, organic phosphates, and chloride ions), crocodilian Hbs exhibit low sensitivity to organic phosphates and high sensitivity to bicarbonate (HCO3(-)), which is believed to augment Hb-O2 unloading during diving and postprandial alkaline tides when blood HCO3(-) levels and metabolic rates increase. Examination of α- and β-globin amino acid sequences of dwarf caiman (Paleosuchus palpebrosus) revealed a unique combination of substitutions at key effector binding sites compared with other vertebrate and crocodilian Hbs: β82Lys→Gln, β143His→Val, and β146His→Tyr. These substitutions delete positive charges and, along with other distinctive changes in residue charge and polarity, may be expected to disrupt allosteric regulation of Hb-O2 affinity. Strikingly, however, P. palpebrosus Hb shows a strong Bohr effect, and marked deoxygenation-linked binding of organic phosphates (ATP and DPG) and CO2 as carbamate (contrasting with HCO3(-) binding in other crocodilians). Unlike other Hbs, it polymerizes to large complexes in the oxygenated state. The highly unusual properties of P. palpebrosus Hb align with a high content of His residues (potential sites for oxygenation-linked proton binding) and distinctive surface Cys residues that may form intermolecular disulfide bridges upon polymerization. On the basis of its singular properties, P. palpebrosus Hb provides a unique opportunity for studies on structure-function coupling and the evolution of compensatory mechanisms for maintaining tissue O2 delivery in Hbs that lack conventional effector-binding residues.

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“…(1) (2) where log P50p and P50a refer to the measurements in the presence and in the absence of ATP, respectively, KD and KO are the ATP association constants for the deoxy and oxyhemoglobins and X is molar concentration of free ATP [15,3].…”

Section: Methodsmentioning

confidence: 99%

“…However, in the presence of organic polyphosphates, such as adenosine triphosphate (ATP) or inositol hexaphosphate (IHP), these hemoglobins show an evident oxygen affinity decrease and a simultaneous increase of the Bohr effect and cooperativity [1,2,3]. The initial proposal was based in the hemoglobins from the semi-aquatic South American snake Liophis miliaris.…”

Section: Introductionmentioning

confidence: 99%

Rattlesnake Hemoglobins: Functional Properties and Tetrameric Stability

Lombardi¹,

Anazetti²,

Santos³

et al. 2006

PPL

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Dimer-tetramer transition in hemoglobins from Liophis miliaris—I. Effect of organic polyphosphates

Cited by 30 publications

References 12 publications

ATP-induced Tetramerization and Cooperativity in Hemoglobin of Lower Vertebrates

ATP-induced Tetramerization and Cooperativity in Hemoglobin of Lower Vertebrates

Lack of conventional oxygen-linked proton and anion binding sites does not impair allosteric regulation of oxygen binding in dwarf caiman hemoglobin

Rattlesnake Hemoglobins: Functional Properties and Tetrameric Stability

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