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.
Comments: Comment in: Nat Struct Biol 1996
