Molecular Code for Cooperativity in Hemoglobin

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 in...

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Published in:Science (American Association for the Advancement of Science) 1992-01, Vol.255 (5040), p.54-63
Main Authors: Ackers, Gary K., Doyle, Michael L., Myers, David, Daugherty, Margaret A.
Format: Article
Language:English
Subjects:
allosteric properties
Allosteric Regulation
Analytical, structural and metabolic biochemistry
Biochemistry
Biological and medical sciences
Biological control systems
Blood
Calorimetry
Cellular biology
Circular Dichroism
Cooperation
cooperativity
Dimers
Energy
Free energy
Fundamental and applied biological sciences. Psychology
haemoglobin
Hemoglobin
Hemoglobins
Hemoglobins - chemistry
Hemoglobins - genetics
Hemoglobins - metabolism
Hemoproteins
Hybridity
intermediates
Kinetics
Ligands
Ligation
Macromolecular Substances
Metalloproteins
Models, Molecular
Molecular structure
Molecules
Mutation
Oxyhemoglobins - chemistry
Oxyhemoglobins - metabolism
Physiological regulation
Protein Conformation
Proteins
reviews
Thermodynamics
Tissue oxygenation
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cited_by cdi_FETCH-LOGICAL-c771t-1b2d50efaae9cea2ed2ba0759afb71c38ec34a0ca9e6bde1e6da4f94182406f03
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container_issue 5040
container_start_page 54
container_title Science (American Association for the Advancement of Science)
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creator Ackers, Gary K.
Doyle, Michael L.
Myers, David
Daugherty, Margaret A.
description 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.
doi_str_mv 10.1126/science.1553532
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Binding affinity is regulated through a hierarchical code of tertiary-quaternary coupling that includes the classical allosteric models as limiting cases.</description><identifier>ISSN: 0036-8075</identifier><identifier>EISSN: 1095-9203</identifier><identifier>DOI: 10.1126/science.1553532</identifier><identifier>PMID: 1553532</identifier><identifier>CODEN: SCIEAS</identifier><language>eng</language><publisher>Washington, DC: American Society for the Advancement of Science</publisher><subject>allosteric properties ; Allosteric Regulation ; Analytical, structural and metabolic biochemistry ; Biochemistry ; Biological and medical sciences ; Biological control systems ; Blood ; Calorimetry ; Cellular biology ; Circular Dichroism ; Cooperation ; cooperativity ; Dimers ; Energy ; Free energy ; Fundamental and applied biological sciences. 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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. 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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.</abstract><cop>Washington, DC</cop><pub>American Society for the Advancement of Science</pub><pmid>1553532</pmid><doi>10.1126/science.1553532</doi><tpages>10</tpages></addata></record>
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subjects allosteric properties
Allosteric Regulation
Analytical, structural and metabolic biochemistry
Biochemistry
Biological and medical sciences
Biological control systems
Blood
Calorimetry
Cellular biology
Circular Dichroism
Cooperation
cooperativity
Dimers
Energy
Free energy
Fundamental and applied biological sciences. Psychology
haemoglobin
Hemoglobin
Hemoglobins
Hemoglobins - chemistry
Hemoglobins - genetics
Hemoglobins - metabolism
Hemoproteins
Hybridity
intermediates
Kinetics
Ligands
Ligation
Macromolecular Substances
Metalloproteins
Models, Molecular
Molecular structure
Molecules
Mutation
Oxyhemoglobins - chemistry
Oxyhemoglobins - metabolism
Physiological regulation
Protein Conformation
Proteins
reviews
Thermodynamics
Tissue oxygenation
title Molecular Code for Cooperativity in Hemoglobin
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