Determination of the dipole moments of RNAse SA wild type and a basic mutant

Chari, Ravi; Singh, Shubhadra N.; Yadav, Sandeep; Brems, David N.; Kalonia, Devendra S.

doi:10.1002/prot.24006

Cited by 8 publications

(6 citation statements)

References 42 publications

(67 reference statements)

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“…Values for the parameter (κ + 2)CM are given in Table 1, based on values of ∆ε/C p obtained experimentally [56][57][58][59][60][61][62] for a range of globular proteins. No obvious relationship can be seen to link the value of a protein's effective polarization factor (κ + 2)CM (per unit volume) with its molecular weight.…”

Section: Empirical Relationship Connecting Clausius-mossotti (Cm) and The β-Dispersionmentioning

confidence: 99%

Protein Dielectrophoresis: I. Status of Experiments and an Empirical Theory

2020

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The dielectrophoresis (DEP) data reported in the literature since 1994 for 22 different globular proteins is examined in detail. Apart from three cases, all of the reported protein DEP experiments employed a gradient field factor ∇ E m 2 that is much smaller (in some instances by many orders of magnitude) than the ~4 × 1021 V2/m3 required, according to current DEP theory, to overcome the dispersive forces associated with Brownian motion. This failing results from the macroscopic Clausius–Mossotti (CM) factor being restricted to the range 1.0 > CM > −0.5. Current DEP theory precludes the protein’s permanent dipole moment (rather than the induced moment) from contributing to the DEP force. Based on the magnitude of the β-dispersion exhibited by globular proteins in the frequency range 1 kHz–50 MHz, an empirically derived molecular version of CM is obtained. This factor varies greatly in magnitude from protein to protein (e.g., ~37,000 for carboxypeptidase; ~190 for phospholipase) and when incorporated into the basic expression for the DEP force brings most of the reported protein DEP above the minimum required to overcome dispersive Brownian thermal effects. We believe this empirically-derived finding validates the theories currently being advanced by Matyushov and co-workers.

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Section: Empirical Relationship Connecting Clausius-mossotti (Cm) and The β-Dispersionmentioning

confidence: 99%

Protein Dielectrophoresis: I. Status of Experiments and an Empirical Theory

2020

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“…However, care must be taken when engineering in charged mutations. If the protein net charge is close to zero, an anisotropic charge distribution can cause protein self association [13,14,71,99], which has been correlated with increased aggregation propensity [55,80]. To avoid increasing protein charge anisotropy, charged mutations should carry the same sign as the net charge on the corresponding protein scaffold [31,100].…”

Section: Introductionmentioning

confidence: 99%

The effect of charge mutations on the stability and aggregation of a human single chain Fv fragment

Austerberry

Dajani

Panova

et al. 2017

European Journal of Pharmaceutics and Biopharmaceutics

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a b s t r a c tThe aggregation propensities for a series of single-chain variable fragment (scFv) mutant proteins containing supercharged sequences, salt bridges and lysine/arginine-enriched motifs were characterised as a function of pH and ionic strength to isolate the electrostatic contributions. Recent improvements in aggregation predictors rely on using knowledge of native-state protein-protein interactions. Consistent with previous findings, electrostatic contributions to native protein-protein interactions correlate with aggregate growth pathway and rates. However, strong reversible self-association observed for selected mutants under native conditions did not correlate with aggregate growth, indicating 'sticky' surfaces that are exposed in the native monomeric state are inaccessible when aggregates grow. We find that even though similar native-state protein-protein interactions occur for the arginine and lysine-enriched mutants, aggregation propensity is increased for the former and decreased for the latter, providing evidence that lysine suppresses interactions between partially folded states under these conditions. The supercharged mutants follow the behaviour observed for basic proteins under acidic conditions; where excess net charge decreases conformational stability and increases nucleation rates, but conversely reduces aggregate growth rates due to increased intermolecular electrostatic repulsion. The results highlight the limitations of using conformational stability and native-state protein-protein interactions as predictors for aggregation propensity and provide guidance on how to engineer stabilizing charged mutations.

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“…Chari et al . (2012) determined experimentally the dipole moment of RNase by measuring solution capacitance and there are other specialized theoretical studies applied to secondary structures (Hol, 1985; Sengupta et al ., 2005).…”

Section: Moment Vectors and Energiesmentioning

confidence: 99%

Use of vector formalism in the analysis of hydrophobic and electric driving forces in biological assemblies

Mozo-Villarías

Cedano

Querol

2022

Quart. Rev. Biophys.

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Hydrophobic forces are known to have a crucial part not only in the conformation of the three-dimensional structure of proteins, but also in the build-up of DNA–protein complexes. Electric forces also play an important role both in the tertiary as well in the quaternary structure of macromolecular associations. Sometimes both hydrophobic and electric interactions add up their strengths to accomplish these structures but in most cases they act in opposite directions. This fact, together with being overall interactions with different ranges, provides a nuanced equilibrium also modulated by the need to comply with steric hindrances and geometric frustration effects. This review focuses on the utility of using the hydrophobic and electrical dipole moment vectors to describe the interactions that give rise to the structures of biological macromolecules. Although different definitions of both electric dipole and hydrophobic moments have been described in the literature, results obtained in biological assemblies demonstrate the principle of the biological membrane model. According to this model, postulated by our group, biological macromolecules tend to associate by aligning their hydrophobic moments in a similar manner to phospholipids in a membrane. Examples of both closed and open structures are used to assess the predictability of our model. We seek agreement between our results with those described in the current literature. The review ends with possible future projections using this formalism.

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Determination of the dipole moments of RNAse SA wild type and a basic mutant

Cited by 8 publications

References 42 publications

Protein Dielectrophoresis: I. Status of Experiments and an Empirical Theory

Protein Dielectrophoresis: I. Status of Experiments and an Empirical Theory

The effect of charge mutations on the stability and aggregation of a human single chain Fv fragment

Use of vector formalism in the analysis of hydrophobic and electric driving forces in biological assemblies

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