The pathway of allosteric control as revealed by hemoglobin intermediate states.
The energetics of hemoglobin cooperativity has been analyzed through the use of stable, partially-ligated intermediates. These studies revealed that the two dimeric halves of the tetramer are autonomous, leading to a Symmetry Rule that governs the relationship between ligand-binding and the T-->R quaternary switch: the R structure is favored over T only when ligands are bound to both dimers within the tetramer. A major feature of the Symmetry Rule mechanism is the generation of cooperative free energy by tertiary conformational constraints, which are formed within one dimeric half of the T-tetramer and released during the quaternary structure change to R. These rules of tertiary and quaternary molecular switching also govern the roles of the heterotropic allosteric effectors (e.g. Bohr protons).
Holt
J M
JM
Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Ackers
G K
GK
D000494:Allosteric Regulation; D000595:Amino Acid Sequence; D000818:Animals; D006454:Hemoglobins / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D046911:Macromolecular Substances; D008958:Models, Molecular; D008961:Models, Structural; D010108:Oxyhemoglobins / Q000737:chemistry / Q000378:metabolism; D017354:Point Mutation; D011487:Protein Conformation; D017434:Protein Structure, Tertiary
D006454:Hemoglobins; D046911:Macromolecular Substances; D010108:Oxyhemoglobins