Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Science 3 January 1992:
Vol. 255. no. 5040, pp. 54 - 63
DOI: 10.1126/science.1553532
Prev | Table of Contents | Next

Articles

Science, Vol 255, Issue 5040, 54-63
Copyright © 1992 by American Association for the Advancement of Science

articles

Molecular code for cooperativity in hemoglobin

GK Ackers, ML Doyle, D Myers, and MA Daugherty

Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO 63110.

Although tetrameric hemoglobin has been studied extensively as a prototype for understanding mechanisms of allosteric regulation, the functional and structural properties of its eight intermediate ligation forms have remained elusive. Recent experiments on the energetics of cooperativity of these intermediates, along with assignments of their quaternary structures, have revealed that the allosteric mechanism is controlled by a previously unrecognized symmetry feature: quaternary switching from form T to form R occurs whenever heme-site binding creates a tetramer with at least one ligated subunit on each dimeric half-molecule. This "symmetry rule" translates the configurational isomers of heme-site ligation into six observed switchpoints of quaternary transition. Cooperativity arises from both "concerted" quaternary switching and "sequential" modulation of binding within each quaternary form, T and R. Binding affinity is regulated through a hierarchical code of tertiary-quaternary coupling that includes the classical allosteric models as limiting cases.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Molecular Recognition and Self-Assembly Special Feature: Squaring cooperative binding circles.
A. B. C. Deutman, C. Monnereau, M. Moalin, R. G. E. Coumans, N. Veling, M. Coenen, J. M. M. Smits, R. de Gelder, J. A. A. W. Elemans, G. Ercolani, et al. (2009)
PNAS 106, 10471-10476
   Abstract »    Full Text »    PDF »
A quantum-chemical picture of hemoglobin affinity.
R. E. Alcantara, C. Xu, T. G. Spiro, and V. Guallar (2007)
PNAS 104, 18451-18455
   Abstract »    Full Text »    PDF »
Inhibiting HIV-1 integrase by shifting its oligomerization equilibrium.
Z. Hayouka, J. Rosenbluh, A. Levin, S. Loya, M. Lebendiker, D. Veprintsev, M. Kotler, A. Hizi, A. Loyter, and A. Friedler (2007)
PNAS 104, 8316-8321
   Abstract »    Full Text »    PDF »
How the body controls brain temperature: the temperature shielding effect of cerebral blood flow.
M. Zhu, J. J. H. Ackerman, A. L. Sukstanskii, and D. A. Yablonskiy (2006)
J Appl Physiol 101, 1481-1488
   Abstract »    Full Text »    PDF »
Theoretical model of temperature regulation in the brain during changes in functional activity.
A. L. Sukstanskii and D. A. Yablonskiy (2006)
PNAS 103, 12144-12149
   Abstract »    Full Text »    PDF »
Asymmetric Cooperativity in a Symmetric Tetramer: Human Hemoglobin.
G. K. Ackers and J. M. Holt (2006)
J. Biol. Chem. 281, 11441-11443
   Full Text »    PDF »
Single residue modification of only one dimer within the hemoglobin tetramer reveals autonomous dimer function.
G. K. Ackers, P. M. Dalessio, G. H. Lew, M. A. Daugherty, and J. M. Holt (2002)
PNAS 99, 9777-9782
   Abstract »    Full Text »    PDF »
G Protein-Coupled Receptor Allosterism and Complexing.
A. Christopoulos and T. Kenakin (2002)
Pharmacol. Rev. 54, 323-374
   Abstract »    Full Text »    PDF »
Hybrid Tetramers of Porcine Liver Fructose-1,6-bisphosphatase Reveal Multiple Pathways of Allosteric Inhibition.
S. W. Nelson, R. B. Honzatko, and H. J. Fromm (2002)
J. Biol. Chem. 277, 15539-15545
   Abstract »    Full Text »    PDF »
Energetics by NMR: Site-specific binding in a positively cooperative system.
G. P. Tochtrop, K. Richter, C. Tang, J. J. Toner, D. F. Covey, and D. P. Cistola (2002)
PNAS 99, 1847-1852
   Abstract »    Full Text »    PDF »
Coupling between changes in human brain temperature and oxidative metabolism during prolonged visual stimulation.
D. A. Yablonskiy, J. J. H. Ackerman, and M. E. Raichle (2000)
PNAS 97, 7603-7608
   Abstract »    Full Text »    PDF »
Coupling of the Oxygen-linked Interaction Energy for Inositol Hexakisphosphate and Bezafibrate Binding to Human HbA0.
M. Coletta, M. Angeletti, P. Ascenzi, A. Bertollini, S. Della Longa, G. De Sanctis, A. M. Priori, R. Santucci, and G. Amiconi (1999)
J. Biol. Chem. 274, 6865-6874
   Abstract »    Full Text »    PDF »
CO Ligation Intermediates and the Mechanism of Hemoglobin Cooperativity.
M. Perrella and E. Di Cera (1999)
J. Biol. Chem. 274, 2605-2608
   Abstract »    Full Text »    PDF »
Rate Constants for O2 and CO Binding to the alpha  and beta  Subunits within the R and T States of Human Hemoglobin.
S. Unzai, R. Eich, N. Shibayama, J. S. Olson, and H. Morimoto (1998)
J. Biol. Chem. 273, 23150-23159
   Abstract »    Full Text »    PDF »
Normal and Abnormal Protein Subunit Interactions in Hemoglobins.
J. M. Manning, A. Dumoulin, X. Li, and L. R. Manning (1998)
J. Biol. Chem. 273, 19359-19362
   Full Text »    PDF »
Kinetic Structure of Large-Conductance Ca2+-activated K+ Channels Suggests that the Gating Includes Transitions through Intermediate or Secondary States: A Mechanism for Flickers.
B. S. Rothberg and K. L. Magleby (1998)
J. Gen. Physiol. 111, 751-780
   Abstract »    Full Text »    PDF »
T State Hemoglobin Binds Oxygen Noncooperatively with Allosteric Effects of Protons, Inositol Hexaphosphate, and Chloride.
S. Bettati and A. Mozzarelli (1997)
J. Biol. Chem. 272, 32050-32055
   Abstract »    Full Text »    PDF »
The Anodic Hemoglobin of Anguilla anguilla. MOLECULAR BASIS FOR ALLOSTERIC EFFECTS IN A ROOT-EFFECT HEMOGLOBIN.
A. Fago, E. Bendixen, H. Malte, and R. E. Weber (1997)
J. Biol. Chem. 272, 15628-15635
   Abstract »    Full Text »    PDF »
The rational design of allosteric interactions in a monomeric protein and its applications to the construction of biosensors.
J. S. Marvin, E. E. Corcoran, N. A. Hattangadi, J. V. Zhang, S. A. Gere, and H. W. Hellinga (1997)
PNAS 94, 4366-4371
   Abstract »    Full Text »    PDF »
Ligand Linked Assembly of Scapharca Dimeric Hemoglobin.
W. E. Royer Jr., R. A. Fox, F. R. Smith, D. Zhu, and E. H. Braswell (1997)
J. Biol. Chem. 272, 5689-5694
   Abstract »    Full Text »    PDF »
Additivity Principles in Biochemistry.
K. A. Dill and K. A. Dill (1997)
J. Biol. Chem. 272, 701-704
   Full Text »    PDF »
Functional Studies and Polymerization of Recombinant Hemoglobin Glu-alpha 2beta 26(A3) right-arrow Val/Glu-7(A4) right-arrow Ala.
S. Lesecq, V. Baudin, J. Kister, M. C. Marden, C. Poyart, and J. Pagnier (1996)
J. Biol. Chem. 271, 17211-17214
   Abstract »    Full Text »    PDF »
Oxygen Equilibrium Properties of Chromium(III)-Iron(II) Hybrid Hemoglobins.
S. Unzai, H. Hori, G. Miyazaki, N. Shibayama, and H. Morimoto (1996)
J. Biol. Chem. 271, 12451-12456
   Abstract »    Full Text »    PDF »
Probing the alpha(1)beta(2) Interface of Human Hemoglobin by Mutagenesis.
B. Vallone, A. Bellelli, A. E. Miele, M. Brunori, and G. Fermi (1996)
J. Biol. Chem. 271, 12472-12480
   Abstract »    Full Text »    PDF »
Effects of Assembly and Mutations Outside the Active Site on the Functional pH Dependence of Escherichia coli Aspartate Transcarbamylase.
X. Yuan, V. J. LiCata, and N. M. Allewell (1996)
J. Biol. Chem. 271, 1285-1294
   Abstract »    Full Text »    PDF »
Hemoglobin allostery: resonance Raman spectroscopy of kinetic intermediates.
V Jayaraman, K. Rodgers, I Mukerji, and T. Spiro (1995)
Science 269, 1843-1848
   Abstract »    PDF »
Rat Liver ATP Synthase.
P. L. Pedersen, J. Hullihen, M. Bianchet, L. M. Amzel, and M. S. Lebowitz (1995)
J. Biol. Chem. 270, 1775-1784
   Abstract »    Full Text »    PDF »
Nanosecond dynamics of the R-->T transition in hemoglobin: ultraviolet Raman studies.
K. Rodgers and T. Spiro (1994)
Science 265, 1697-1699
   Abstract »    PDF »
Hydrogen Exchange Measurement of the Free Energy of Structural and Allosteric Change in Hemoglobin.
S. W. Englander, J. J. Englander, R. E. McKinnie, G. K. Ackers, G. J. Turner, J. A. Westrick, and S. J. Gill (1992)
Science 256, 1684-1687
   Abstract »    PDF »
The Bohr Effect of Hemoglobin Intermediates and the Role of Salt Bridges in the Tertiary/Quaternary Transitions.
R. Russo, L. Benazzi, and M. Perrella (2001)
J. Biol. Chem. 276, 13628-13634
   Abstract »    Full Text »    PDF »
The Contribution of the Asymmetric alpha 1beta 1 Half-oxygenated Intermediate to Human Hemoglobin Cooperativity.
K.-M. Yun, H. Morimoto, and N. Shibayama (2002)
J. Biol. Chem. 277, 1878-1883
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)