Molecular code for cooperativity in hemoglobin.

G K Ackers; M L Doyle; D Myers; M A Daugherty

doi:10.1126/science.1553532

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PubMed · 1553532

Molecular code for cooperativity in hemoglobin.

G K Ackers·M L Doyle·D Myers·M A Daugherty

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Abstract

Although tetrameric hemoglobin has been studied extensively as a prototype for understanding mechanisms of allosteric regulation, the functional and structural properties of its eight intermediate ligation forms have remained elusive. Recent experiments on the energetics of cooperativity of these intermediates, along with assignments of their quaternary structures, have revealed that the allosteric mechanism is controlled by a previously unrecognized symmetry feature: quaternary switching from form T to form R occurs whenever heme-site binding creates a tetramer with at least one ligated subunit on each dimeric half-molecule. This "symmetry rule" translates the configurational isomers of heme-site ligation into six observed switchpoints of quaternary transition. Cooperativity arises from both "concerted" quaternary switching and "sequential" modulation of binding within each quaternary form, T and R. Binding affinity is regulated through a hierarchical code of tertiary-quaternary coupling that includes the classical allosteric models as limiting cases.

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Allosteric Regulation Calorimetry Circular Dichroism Hemoglobins Kinetics Ligands Macromolecular Substances Models, Molecular Mutation Oxyhemoglobins Protein Conformation Thermodynamics Comparative Study Journal Article Research Support, U.S. Gov't, Non-P.H.S.Research Support, U.S. Gov't, P.H.S.

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G K Ackers, M L Doyle, D Myers, M A Daugherty. 1992-01-03. Molecular code for cooperativity in hemoglobin.. https://doi.org/10.1126/science.1553532

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