title: Structural basis for the root effect in haemoglobin.
abstract: The remarkable ability of root effect haemoglobins to pump oxygen against high O2 gradients results from extreme, acid-induced reductions in O2 affinity and cooperativity. The long-sought mechanism for the root effect, revealed by the 2 angstrom crystal structure of the ligand-bound haemoglobin from Leiostomus xanthurus at pH 7.5, unexpectedly involves modulation of the R-state. Key residues strategically assemble positive-charge clusters across the allosteric beta1 beta2-interface in the R-state. At low pH, protonation of the beta N terminus and His 147(HC3)beta within these clusters is postulated to destabilize the R-state and promote the acid-triggered, allosteric R-->T switch with concomitant O2 release. Surprisingly, a set of residues specific to root effect haemoglobins recruit additional residues, conserved among most haemoglobins, to produce the root effect.
authors.affiliation: The Scripps Research Institute, La Jolla, California 92037, USA.
authors.forename: S E
authors.initials: SE
authors.lastname: Mylvaganam
authors.forename: C
authors.initials: C
authors.lastname: Bonaventura
authors.forename: J
authors.initials: J
authors.lastname: Bonaventura
authors.forename: E D
authors.initials: ED
authors.lastname: Getzoff
mesh_terms: D000494:Allosteric Regulation; D000495:Allosteric Site; D000595:Amino Acid Sequence; D000818:Animals; D018360:Crystallography, X-Ray; D004563:Electrochemistry; D005399:Fishes; D006454:Hemoglobins / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D046911:Macromolecular Substances; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity
chemical_list: D006454:Hemoglobins; D046911:Macromolecular Substances