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Steric factors moderate conformational fluidity and contribute to the high proton sensitivity of Root effect hemoglobins.

Publication ,  Journal Article
Bonaventura, C; Henkens, R; Friedman, J; Siburt, CJP; Kraiter, D; Crumbliss, AL
Published in: Biochimica et biophysica acta
October 2011

The structural basis of the extreme pH dependence of oxygen binding to Root effect Hbs is a long-standing puzzle in the field of protein chemistry. A previously unappreciated role of steric factors in the Root effect was revealed by a comparison of pH effects on oxygenation and oxidation processes in human Hb relative to Spot (Leiostomus xanthurus) and Carp (Cyprinodon carpio) Hbs. The Root effect confers five-fold increased pH sensitivity to oxygenation of Spot and Carp Hbs relative to Hb A(0) in the absence of anionic effectors, and even larger relative elevations of pH sensitivity of oxygenation in the presence of 0.2M phosphate. Remarkably, the Root effect was not evident in the oxidation of the Root effect Hbs. This finding rules out pH-dependent alterations in the thermodynamic properties of the heme iron, measured in the anaerobic oxidation reaction, as the basis of the Root effect. The alternative explanation supported by these results is that the elevated pH sensitivity of oxygenation of Root effect Hbs is attributable to globin-dependent steric effects that alter oxygen affinity by constraining conformational fluidity, but which have little influence on electron exchange via the heme edge. This elegant mode of allosteric control can regulate oxygen affinity within a given quaternary state, in addition to modifying the T-R equilibrium. Evolution of Hb sequences that result in proton-linked steric barriers to heme oxygenation could provide a general mechanism to account for the appearance of the Root effect in the structurally diverse Hbs of many species.

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Published In

Biochimica et biophysica acta

DOI

EISSN

1878-2434

ISSN

0006-3002

Publication Date

October 2011

Volume

1814

Issue

10

Start / End Page

1261 / 1268

Related Subject Headings

  • Stereoisomerism
  • Protons
  • Protein Multimerization
  • Protein Folding
  • Protein Conformation
  • Protein Binding
  • Phosphates
  • Oxygen
  • Oxidation-Reduction
  • Organic Chemistry Phenomena
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Bonaventura, C., Henkens, R., Friedman, J., Siburt, C. J. P., Kraiter, D., & Crumbliss, A. L. (2011). Steric factors moderate conformational fluidity and contribute to the high proton sensitivity of Root effect hemoglobins. Biochimica et Biophysica Acta, 1814(10), 1261–1268. https://doi.org/10.1016/j.bbapap.2011.06.012
Bonaventura, Celia, Robert Henkens, Joel Friedman, Claire J Parker Siburt, Daniel Kraiter, and Alvin L. Crumbliss. “Steric factors moderate conformational fluidity and contribute to the high proton sensitivity of Root effect hemoglobins.Biochimica et Biophysica Acta 1814, no. 10 (October 2011): 1261–68. https://doi.org/10.1016/j.bbapap.2011.06.012.
Bonaventura C, Henkens R, Friedman J, Siburt CJP, Kraiter D, Crumbliss AL. Steric factors moderate conformational fluidity and contribute to the high proton sensitivity of Root effect hemoglobins. Biochimica et biophysica acta. 2011 Oct;1814(10):1261–8.
Bonaventura, Celia, et al. “Steric factors moderate conformational fluidity and contribute to the high proton sensitivity of Root effect hemoglobins.Biochimica et Biophysica Acta, vol. 1814, no. 10, Oct. 2011, pp. 1261–68. Epmc, doi:10.1016/j.bbapap.2011.06.012.
Bonaventura C, Henkens R, Friedman J, Siburt CJP, Kraiter D, Crumbliss AL. Steric factors moderate conformational fluidity and contribute to the high proton sensitivity of Root effect hemoglobins. Biochimica et biophysica acta. 2011 Oct;1814(10):1261–1268.

Published In

Biochimica et biophysica acta

DOI

EISSN

1878-2434

ISSN

0006-3002

Publication Date

October 2011

Volume

1814

Issue

10

Start / End Page

1261 / 1268

Related Subject Headings

  • Stereoisomerism
  • Protons
  • Protein Multimerization
  • Protein Folding
  • Protein Conformation
  • Protein Binding
  • Phosphates
  • Oxygen
  • Oxidation-Reduction
  • Organic Chemistry Phenomena