Extending the Pressure–Temperature State Diagram of Myoglobin

Meersman, Filip; Smeller, László; Heremans, Karel

doi:10.1002/hlca.200590037

Cited by 22 publications

(15 citation statements)

References 48 publications

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“…We have shown previously that myoglobin is pressure-stable up to 650 MPa (22,49,50). Our results presented in this paper also show no signs of denaturation in the pressure range up to 250 MPa, as can be seen in the insets of Fig.…”

Section: The Changes In Trp Fluorescence In the Studied Pressure Rangsupporting

confidence: 82%

Allosteric Effectors Influence the Tetramer Stability of Both R- and T-states of Hemoglobin A

Schay

Smeller

Tsuneshige

et al. 2006

Journal of Biological Chemistry

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The contribution of heterotropic effectors to hemoglobin allostery is still not completely understood. With the recently proposed global allostery model, this question acquires crucial significance, because it relates tertiary conformational changes to effector binding in both the R-and T-states. In this context, an important question is how far the induced conformational changes propagate from the binding site(s) of the allosteric effectors. We present a study in which we monitored the interdimeric interface when the effectors such as Cl ؊ , 2,3-diphosphoglycerate, inositol hexaphosphate, and bezafibrate were bound. We studied oxy-Hb and a hybrid form (␣FeO 2 ) 2 -(␤Zn) 2 as the T-state analogue by monitoring heme absorption and Trp intrinsic fluorescence under hydrostatic pressure. We observed a pressure-dependent change in the intrinsic fluorescence, which we attribute to a pressure-induced tetramer to dimer transition with characteristic pressures in the 70 -200-megapascal range. The transition is sensitive to the binding of allosteric effectors. We fitted the data with a simple model for the tetramer-dimer transition and determined the dissociation constants at atmospheric pressure. In the R-state, we observed a stabilizing effect by the allosteric effectors, although in the T-analogue a stronger destabilizing effect was seen. The order of efficiency was the same in both states, but with the opposite trend as inositol hexaphosphate > 2,3-diphosphoglycerate > Cl ؊ . We detected intrinsic fluorescence from bound bezafibrate that introduced uncertainty in the comparison with other effectors. The results support the global allostery model by showing that conformational changes propagate from the effector binding site to the interdimeric interfaces in both quaternary states.Hemoglobin (1) is a tetrameric protein, which plays a vital role in the transport of oxygen. It consists of two dimers of ␣ and ␤ subunits that reversibly bind and release oxygen (1). The description of this cooperative phenomenon has been most frequently derived from the Monod-Wyman-Changeux (MWC) 2 two-state allosteric model (2) that attributes cooperativity to a rapid equilibrium between two conformations of distinct oxygen affinity of the whole tetramer. These distinct states are the fully unliganded T-state and the fully ligated R-state. Szabo and Karplus (3) modified the two-state model incorporating the stereochemical mechanism suggested by Perutz (4) for the T to R switch, and introduced ligation-induced tertiary changes within the T-state. In this extended model (MWC-SK), it was proposed that cooperativity still works through a ligation-induced shift in the equilibrium of states T and R, but the model attributed importance in the conformational switch to certain changes at the inter-and intrasubunit interfaces.

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Section: The Changes In Trp Fluorescence In the Studied Pressure Rangsupporting

confidence: 82%

Allosteric Effectors Influence the Tetramer Stability of Both R- and T-states of Hemoglobin A

Schay

Smeller

Tsuneshige

et al. 2006

Journal of Biological Chemistry

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“…But the suggestion that the most promising candidates are systems with locally tetrahedral molecular structure such as C, SiO 2 and H 2 O (26) makes aqueous solutions of biopolymers with the predominant role of highly directional hydrogen bonding, good candidates. (14,27). An enthalpy-driven or a temperature-induced transition at high pressure might also be expected in these systems but has not been reported so far.…”

Section: Liquid-liquid Transitions In Protein Solutions?mentioning

confidence: 99%

Protein dynamics: hydration and cavities

Heremans

2005

Braz J Med Biol Res

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The temperature-pressure behavior of proteins seems to be unique among the biological macromolecules. Thermodynamic as well as kinetic data show the typical elliptical stability diagram. This may be extended by assuming that the unfolded state gives rise to volume and enthalpy-driven liquid-liquid transitions. A molecular interpretation follows from the temperature and the pressure dependence of the hydration and cavities. We suggest that positron annihilation spectroscopy can provide additional quantitative evidence for the contributions of cavities to the dynamics of proteins. Only mature amyloid fibrils that form from unfolded proteins are very resistant to pressure treatment.

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“…He also analyzed the data obtained on ribonuclease-A by Brandts (Brandts et al 1970). Since then a number of proteins were studied under pressure, and the complete p-T phase diagrams have been determined for several of them (Zipp and Walter 1973;Panick et al 1999;Lassalle et al 2000;Meersman et al 2005;Smeller 2002;Maeno et al 2009;Somkuti et al 2011Somkuti et al , 2012Somkuti et al , 2013a. This review summarizes the present knowledge about the p-T phase diagram of protein unfolding.…”

mentioning

confidence: 97%

“…In the meantime several practical applications appeared: pressure treatment of biological systems, like microorganisms and complex food systems were studied and some of these studies led to the development of products which were successfully commercialized Yamakura et al 2005;Rastogi et al 2007;Yaldagard et al 2008;Knorr et al 2011). Simultaneously more and more proteins were experimentally investigated and characterized under pressure as part of basic research projects (Brandts et al 1970;Hawley 1971;Panick et al 1999;Smeller et al 1999;Lassalle et al 2000;Meersman et al 2002Meersman et al , 2005Smeller 2002Smeller , 2009Maeno et al 2009;Somkuti et al 2012Somkuti et al , 2013a.…”

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confidence: 98%

Protein Denaturation on p-T Axes – Thermodynamics and Analysis

Smeller

2015

Subcellular Biochemistry

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Proteins are essential players in the vast majority of molecular level life processes. Since their structure is in most cases substantial for their correct function, study of their structural changes attracted great interest in the past decades. The three dimensional structure of proteins is influenced by several factors including temperature, pH, presence of chaotropic and cosmotropic agents, or presence of denaturants. Although pressure is an equally important thermodynamic parameter as temperature, pressure studies are considerably less frequent in the literature, probably due to the technical difficulties associated to the pressure studies. Although the first steps in the high-pressure protein study have been done 100 years ago with Bridgman's ground breaking work, the field was silent until the modern spectroscopic techniques allowed the characterization of the protein structural changes, while the protein was under pressure. Recently a number of proteins were studied under pressure, and complete pressure-temperature phase diagrams were determined for several of them. This review summarizes the thermodynamic background of the typical elliptic p-T phase diagram, its limitations and the possible reasons for deviations of the experimental diagrams from the theoretical one. Finally we show some examples of experimentally determined pressure-temperature phase diagrams.

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Extending the Pressure–Temperature State Diagram of Myoglobin

Cited by 22 publications

References 48 publications

Allosteric Effectors Influence the Tetramer Stability of Both R- and T-states of Hemoglobin A

Allosteric Effectors Influence the Tetramer Stability of Both R- and T-states of Hemoglobin A

Protein dynamics: hydration and cavities

Protein Denaturation on p-T Axes – Thermodynamics and Analysis

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