Structural basis for the root effect in haemoglobin

Nat Struct Biol. 1996 Mar;3(3):275-83. doi: 10.1038/nsb0396-275.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Allosteric Regulation
  • Allosteric Site
  • Amino Acid Sequence
  • Animals
  • Crystallography, X-Ray
  • Electrochemistry
  • Fishes
  • Hemoglobins / chemistry*
  • Hemoglobins / metabolism
  • Humans
  • Hydrogen-Ion Concentration
  • Macromolecular Substances
  • Models, Molecular
  • Molecular Sequence Data
  • Sequence Homology, Amino Acid
  • Species Specificity

Substances

  • Hemoglobins
  • Macromolecular Substances

Associated data

  • SWISSPROT/P02016
  • SWISSPROT/P02018
  • SWISSPROT/P02019
  • SWISSPROT/P02020
  • SWISSPROT/P02138
  • SWISSPROT/P02139
  • SWISSPROT/P02140
  • SWISSPROT/P02141
  • SWISSPROT/P02142
  • SWISSPROT/P10777
  • SWISSPROT/P11748
  • SWISSPROT/P11749
  • SWISSPROT/P14520
  • SWISSPROT/P14521
  • SWISSPROT/P14527
  • SWISSPROT/P16308
  • SWISSPROT/P16309
  • SWISSPROT/P23016
  • SWISSPROT/P23017
  • SWISSPROT/P23018
  • SWISSPROT/P23740
  • SWISSPROT/P23741
  • SWISSPROT/P29623
  • SWISSPROT/P29624
  • SWISSPROT/P29625
  • SWISSPROT/P29628