Reaction volume of protonic ionization for buffering agents. Prediction of pressure dependence of pH and pOH

The formation of amyloid aggregates is the hallmark of the amyloidogenic diseases. Transthyretin (TTR) is involved in senile systemic amyloidosis (wild-type protein) and familial amyloidotic polyneuropathy (point mutants). Through the use of high hydrostatic pressure (HHP), we compare the stability among wild-type (wt) TTR, two disease-associated mutations (V30M and L55P) and a trans-suppressor mutation (T119M). Our data show that the amyloidogenic conformation, easily populated in the disease-associated mutant L55P, can be induced by a cycle of compression-decompression with the wt protein rendering the latter highly amyloidogenic. After decompression, the recovered wt structure has weaker subunit interactions (loosened tetramer, T 4 p ) and presents a stability similar to L55P, suggesting that HHP induces a defective fold in the wt protein, converting it to an altered conformation already present in the aggressive mutant, L55P. On the other hand, glucose, a chemical chaperone, can mimic the trans-suppression mutation by stabilizing the native state and by decreasing the amyloidogenic potential of the wt TTR at pH 5.0. The sequence of pressure stability observed was: L55P , V30M , wt p T119M. The pressure dissociation of L55P at 1 8C exhibited dependence on protein concentration, allowing us to assess the volume change of association and the free-energy change. After a cycle of compression-decompression at 37 8C and pH 5.6 or lower, all amyloidogenic variants underwent aggregation. Binding of bis-(8-anilinonaphthalene-1-sulfonate) (bis-ANS) revealed that the species formed under pressure retained part of its tertiary contacts (except T119M). However, at neutral pH, where aggregation did not take place after decompression, bis-ANS binding was absent. Thus, TTR has to experience this partially folded conformation to undergo aggregation after decompression. Overall, our studies provide evidence that amyloidogenesis correlates with less packed structures (larger volume changes) and high susceptibility to water infiltration. The hydration effects can be counteracted by osmolytes or by a specific mutation.

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“…The DV values for the protonic ionization of Mes and Tris are positive and equal 3.9 and 4.3 cm 3 /mol, respectively. 49 …”

Section: Chemicalsmentioning

confidence: 99%

Hydration and Packing are Crucial to Amyloidogenesis as Revealed by Pressure Studies on Transthyretin Variants that Either Protect or Worsen Amyloid Disease

Gonzales

Palmieri

Valory

et al. 2003

Journal of Molecular Biology

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“…The induced charged ions are compact and have less volume. The ionization volume of water is about -22.2 ml/mol at 25°C (Kitamura and Itoh, 1987;Neuman et al, 1973) and could be promoted under pressure. This leads to a pH decrease of 0.7 units at 800 MPa (Heinz, 1997).…”

Section: Discussionmentioning

confidence: 99%

Impact of high hydrostatic pressure on gel formation of low methoxylpectin

Eshtiaghi¹

2013

Afr. J. Pharm. Pharmacol.

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“…Conversely, the pH of a solution buffered by an exothermic buffer rises with increasing pH. Table 1 lists several common buffers for aqueous solutions (King 1969;Disteche 1972;Lo Surdo et al 1979;Kitamura and Itoh 1987;Goldberg et al 2002). As a group, substituted ammonium compounds exhibit substantial positive values of H ion , making them poor choices for DSC experiments.…”

Section: Experimental Conditions For Dscmentioning

confidence: 99%

Probing Solution Thermodynamics by Microcalorimetry

Poon¹

2011

Thermodynamics - Interaction Studies - Solids, Liquids and Gases

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Reaction volume of protonic ionization for buffering agents. Prediction of pressure dependence of pH and pOH

Cited by 210 publications

References 14 publications

Hydration and Packing are Crucial to Amyloidogenesis as Revealed by Pressure Studies on Transthyretin Variants that Either Protect or Worsen Amyloid Disease

Hydration and Packing are Crucial to Amyloidogenesis as Revealed by Pressure Studies on Transthyretin Variants that Either Protect or Worsen Amyloid Disease

Impact of high hydrostatic pressure on gel formation of low methoxylpectin

Probing Solution Thermodynamics by Microcalorimetry

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