Structural basis for the root effect in haemoglobin.

S E Mylvaganam; C Bonaventura; J Bonaventura; E D Getzoff

doi:10.1038/nsb0396-275

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PubMed · 8605630

Structural basis for the root effect in haemoglobin.

S E Mylvaganam·C Bonaventura·J Bonaventura·E D Getzoff

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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.

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Allosteric Regulation Allosteric Site Amino Acid Sequence Animals Crystallography, X-Ray Electrochemistry Fishes Hemoglobins Humans Hydrogen-Ion Concentration Macromolecular Substances Models, Molecular Molecular Sequence Data Sequence Homology, Amino Acid Species Specificity Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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S E Mylvaganam, C Bonaventura, J Bonaventura, E D Getzoff. 1996. Structural basis for the root effect in haemoglobin.. https://doi.org/10.1038/nsb0396-275

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