Compressibility of protein transitions

Taulier, Nicolas; Chalikian, Tigran V.

doi:10.1016/s0167-4838(01)00334-x

Cited by 151 publications

(198 citation statements)

References 140 publications

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“…The magnitude and sign of Δβ T for partial and complete unfolding of proteins is still a matter of debate, even for proteins of similar size, and likely depends on individual cases (42). Nevertheless, the negative signs of Δβ T found for the N ⇌ U and N ⇌ I equilibria are in agreement with those predicted for Δβ S (adiabatic compressibility) (43), which is similar to Δβ T near room temperature (44).…”

Section: Manipulating Populations Of Protein Conformational Substatessupporting

confidence: 70%

High-pressure EPR reveals conformational equilibria and volumetric properties of spin-labeled proteins

McCoy

Hubbell

2011

Proc. Natl. Acad. Sci. U.S.A.

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Identifying equilibrium conformational exchange and characterizing conformational substates is essential for elucidating mechanisms of function in proteins. Site-directed spin labeling has previously been employed to detect conformational changes triggered by some event, but verifying conformational exchange at equilibrium is more challenging. Conformational exchange (microsecond-millisecond) is slow on the EPR time scale, and this proves to be an advantage in directly revealing the presence of multiple substates as distinguishable components in the EPR spectrum, allowing the direct determination of equilibrium constants and free energy differences. However, rotameric exchange of the spin label side chain can also give rise to multiple components in the EPR spectrum. Using spin-labeled mutants of T4 lysozyme, it is shown that high-pressure EPR can be used to: (i) demonstrate equilibrium between spectrally resolved states, (ii) aid in distinguishing conformational from rotameric exchange as the origin of the resolved states, and (iii) determine the relative partial molar volume (ΔV o ) and isothermal compressibility (Δβ T ) of conformational substates in two-component equilibria from the pressure dependence of the equilibrium constant. These volumetric properties provide insight into the structure of the substates. Finally, the pressure dependence of internal side-chain motion is interpreted in terms of volume fluctuations on the nanosecond time scale, the magnitude of which may reflect local backbone flexibility.P roteins undergo structural fluctuations that span a wide range of time scales. Among these motions are fast backbone fluctuations on the picosecond-nanosecond time scale and slower conformational fluctuations on the microsecond and longer time scale (1-3). Molecular flexibility on these time scales plays a central role in protein function (4). For example, in recognitionbinding sequences, dynamic disorder on the nanosecond-microsecond time scale may increase the rate of protein-protein interactions via a "fly casting" mechanism (5). An emerging disorder-to-order paradigm for interaction (6) can also give rise to promiscuity in binding that increases the size of the "interactome."Regulation of protein function is often linked to a conformational switch triggered by an interaction with a chemical or physical signal. One mechanistic interpretation of this event is provided by a "preequilibrium" model, which posits that all possible conformations of a protein exist at equilibrium with populations proportional to their relative energies (7). The exchange ("hopping") event between different conformers is characterized by lifetimes in the microsecond-millisecond range (1, 2, 8). In this model, a conformational switch is viewed as a shift in the relative populations of existing conformational states rather than the creation of a new state.To evaluate the above models and elucidate molecular mechanisms of protein function, it is essential to have experimental means for identifying dynamically disordered sequenc...

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Section: Manipulating Populations Of Protein Conformational Substatessupporting

confidence: 70%

High-pressure EPR reveals conformational equilibria and volumetric properties of spin-labeled proteins

McCoy

Hubbell

2011

Proc. Natl. Acad. Sci. U.S.A.

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“…However, experimental measurement of this parameter of proteins in a dilute solution is quite difficult. Indeed, this quantity has been determined indirectly from the theoretical equation using the adiabatic compressibility of a protein solution, which was determined by the sound velocity in the solution (26)(27)(28)(29)(30)(31). Although the relation between volume fluctuations and isothermal compressibility is rigorously correct only with respect to the intrinsic part of the volume compressibility, and not the partial molar volume compressibility (32), we considered that this partial molar volume compressibility is still useful for characterizing the fluctuation of the protein structure including its interacting water molecules.…”

Section: Significancementioning

confidence: 99%

Transient conformational fluctuation of TePixD during a reaction

Kuroi

Okajima

Ikeuchi

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Knowledge of the dynamical behavior of proteins, and in particular their conformational fluctuations, is essential to understanding the mechanisms underlying their reactions. Here, transient enhancement of the isothermal partial molar compressibility, which is directly related to the conformational fluctuation, during a chemical reaction of a blue light sensor protein from the thermophilic cyanobacterium Thermosynechococcus elongatus BP-1 (TePixD, Tll0078) was investigated in a time-resolved manner. The UV-Vis absorption spectrum of TePixD did not change with the application of high pressure. Conversely, the transient grating signal intensities representing the volume change depended significantly on the pressure. This result implies that the compressibility changes during the reaction. From the pressure dependence of the amplitude, the compressibility change of two short-lived intermediate (I 1 and I 2 ) states were determined to be +(5.6 ± 0.6) × 10 −2 cm 3 ·mol −1 ·MPa −1 for I 1 and +(6.6 ± 0.7)×10 −2 cm 3 ·mol −1 ·MPa −1 for I 2 . This result showed that the structural fluctuation of intermediates was enhanced during the reaction. To clarify the relationship between the fluctuation and the reaction, the compressibility of multiply excited TePixD was investigated. The isothermal compressibility of I 1 and I 2 intermediates of TePixD showed a monotonic decrease with increasing excitation laser power, and this tendency correlated with the reactivity of the protein. This result indicates that the TePixD decamer cannot react when its structural fluctuation is small. We concluded that the enhanced compressibility is an important factor for triggering the reaction of TePixD. To our knowledge, this is the first report showing enhanced fluctuations of intermediate species during a protein reaction, supporting the importance of fluctuations. P roteins often transfer information through changes in domaindomain (or intermolecular) interactions. Photosensor proteins are an important example. They have light-sensing domains and function by using the light-driven changes in domain-domain interactions (1). The sensor of blue light using FAD (BLUF) domain is a light-sensing module found widely among the bacterial kingdom (2). The BLUF domain initiates its photoreaction by the light excitation of the flavin moiety inside the protein, which changes the domain-domain interaction, causing a quaternary structural change and finally transmitting biological signals (3, 4). It has been an important research topic to elucidate how the initial photochemistry occurring in the vicinity of the chromophore leads to the subsequent large conformation change in other domains, which are generally apart from the chromophore.It may be reasonable to consider that the conformation change in the BLUF domain is the driving force in its subsequent reaction; that is, the change in domain-domain interaction. However, sometimes, clear conformational changes have not been observed for the BLUF domain; its conformation is very similar before and after p...

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“…This contribution results from proton transfer reactions accompanying protonation/ deprotonation of titrable amino acids, which also cause a relaxation increase in ultrasonic absorption. 26,[53][54][55][56] The relaxation contribution to relative molar sound velocity increment, D[u] rel ¼ ÀD() rel / (2!c), can be calculated from the relaxation increase in ultrasonic absorption expressed per wavelength, D() rel ( is the coefficient of ultrasonic absorption; is the ultrasonic wavelength; ! is the angular frequency of ultrasound; and is the relaxation time of the proton-transfer reaction).…”

Section: Resultsmentioning

confidence: 99%

“…25,26,28,49,59 The hydration change in compressibility, Dk h , results from exposure to the solvent of previously buried atomic groups, as well as from the differential intensity of solute-solvent interactions in the native and denatured conformational states. 25,26 The intrinsic change in compressibility, k M , results from the change in the size of the solvent-inaccessible protein interior as well as in the packing of atomic groups within that interior. 25,26 Based on this conceptual foundation, we have developed a simple model that analytically relates a change in compressibility accompanying a conformational transition of a protein, Dk S , to the degree of its unfolding, .…”

Section: Analysis Of Compressibility Datamentioning

confidence: 99%

“…This deficiency is unfortunate since volume and compressibility are useful thermodynamic parameters that shed light into the hydration properties and intrinsic packing of various conformational states proteins. [25][26][27][28][29][30][31][32][33][34] In this work, we report pH-and salt-dependent data on sound velocity and density of apomyoglobin solutions in the presence of NaCl and NaTCA. We use these data to evaluate changes in sound velocity, volume, and adiabatic compressibility accompanying the native-to-molten globule, molten globuleto-unfolded, molten globule-to-molten globule, and unfolded-to-molten globule transitions of apomyoglobin.…”

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confidence: 99%

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Compressibility changes accompanying conformational transitions of apomyoglobin

2005

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We used high-precision density and ultrasonic velocity measurements to characterize the native (N), molten globule (MG), and unfolded (U) conformations of apomyoglobin. The molten globule states that were studied in this work include the MG(pH4)(NaCl) state observed at pH 4 and 20 mM NaCl, the MG(pH4)(NaTCA) state observed at pH 4 and 20 mM sodium trichloracetate (NaTCA), the MG(pH2)(NaCl) state observed at pH 2 and 200 mM NaCl, and the MG(pH2)(NaTCA) state observed at pH 2 and 20 mM NaTCA. We used our densimetric and acoustic data to evaluate changes in adiabatic compressibility associated with the acid- or salt-induced N-to-MG, MG-to-U, MG-to-MG, and U-to-MG transitions of the protein. The N-to-MG(pH4)(NaCl) and N-to-MG(pH4)(NaTCA) transitions are accompanied by decreases in compressibility of -(3.0 +/- 0.6) x 10(-6) and -(2.0 +/- 0.6) x 10(-6) cm3 g(-1)bar(-1), respectively. The N-to-MG(pH2)(NaCl) and N-to-MG(pH2)(NaTCA) transitions are associated with compressibility changes of -(4.9 +/- 1.1) x 10(-6) and (0.7 +/- 0.9) x 10(-6) cm3 g(-1) bar(-1), respectively. We interpret these data in terms of the degree of unfolding of the various molten globule forms of apomyoglobin. In general, our compressibility data reveal significant disparities between the various equilibrium molten globule states of apomyoglobin while also quantitatively characterizing each of these states. Volumetric insights provided by our data facilitate gaining a better understanding of the folding pathways, intermediates, and kinetics of apomyoglobin folding.

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Compressibility of protein transitions

Cited by 151 publications

References 140 publications

High-pressure EPR reveals conformational equilibria and volumetric properties of spin-labeled proteins

High-pressure EPR reveals conformational equilibria and volumetric properties of spin-labeled proteins

Transient conformational fluctuation of TePixD during a reaction

Compressibility changes accompanying conformational transitions of apomyoglobin

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