Structural basis for the Root effect in haemoglobin


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 Å 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 β1β2-interface in the R-state. At low βH, protonation of the βN terminus and His 147(HC3)β 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.

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Mylvaganam, S., Bonaventura, C., Bonaventura, J. et al. Structural basis for the Root effect in haemoglobin. Nat Struct Mol Biol 3, 275–283 (1996).

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