ATP-induced tetramerization and cooperativity in hemoglobin of lower vertebrates.
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.
Bonafe
C F
CF
Departamento de Bioquímica, Instituto de Biologia, Universidade Estadual de Campinas, 13083-970, Campinas, São Paulo, Brazil.
Matsukuma
A Y
AY
Matsuura
M S
MS
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D005260:Female; D006454:Hemoglobins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D008956:Models, Chemical; D008970:Molecular Weight; D010755:Organophosphates / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D011487:Protein Conformation; D012911:Snakes
D006454:Hemoglobins; D010755:Organophosphates; D000255:Adenosine Triphosphate; C100003:deoxyhemoglobin; D010100:Oxygen