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Structural basis for the Root effect in haemoglobin

Nature Structural Biology volume 3, pages 275–283 (1996)Cite this article

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 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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Authors and Affiliations

  1. The Scripps Research Institute, 10666 N. Torrey Pines Rd, La Jolla, California, 92037, USA

    Shankari E. Mylvaganam & Elizabeth D. Getzoff

  2. Duke University Marine Laboratory, Beaufort, North Carolina, 28516, USA

    Celia Bonaventura & Joseph Bonaventura

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  3. Joseph Bonaventura
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  4. Elizabeth D. Getzoff
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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). https://doi.org/10.1038/nsb0396-275

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