Factors defining the effects of macromolecular crowding on dynamics and thermodynamic stability of heme proteins in-vitro

Kumar, Rajesh; Sharma, Deepak; Kumar, Vinay

doi:10.1016/j.abb.2018.07.018

Cited by 9 publications

(6 citation statements)

References 119 publications

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“…The extent of the destabilizing effect of SNPs on oxyHb (ΔΔ H u ′ = −4.0 kJ mol –1 ) is of the same order of magnitude (a few kJ mol –1 ) as the data reported by Kumar et al and Christiansen et al for enthalpy-driven and entropy-driven macromolecular crowding effects, respectively. , …”

Section: Resultssupporting

confidence: 76%

“…70 The extent of the destabilizing effect of SNPs on oxyHb (ΔΔHu' = -4.0 kJ.mol -1 ) is of the same order of magnitude (a few kJ.mol -1 ) as the data reported by Kumar et al and Christiansen et al for enthalpy-driven and entropy-driven macromolecular crowding effects respectively. 71,72 Whether the destabilization effects of SNPs on oxyHb and the formation of the soft corona could be described as enthalpy-driven macromolecular crowding effect remains to be elucidated. However, we can advance that nanoparticles are as diverse as other solutes in terms of their effects on protein stabilization or destabilization.…”

Section: Snps Stabilize Partially Unfolded Conformationsmentioning

confidence: 99%

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In Situ Analysis of Weakly Bound Proteins Reveals Molecular Basis of Soft Corona Formation

et al. 2020

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Few experimental techniques allow the analysis of the protein corona in situ. As a result, little is known on the effects of nanoparticles on weakly bound proteins that form the soft corona. Despite its biological importance, our understanding of the molecular bases driving its formation is limited. Here we show that hemoglobin can form either a hard or a soft corona on silica nanoparticles depending on the pH conditions. Using cryoTEM and synchrotron-radiation circular dichroism, we show that nanoparticles alter the structure and the stability of weakly bound proteins in situ. Molecular dynamics simulation identified the structural elements driving protein-nanoparticle interaction. Based on thermodynamic analysis, we show that nanoparticles stabilize partially unfolded protein conformations by enthalpy-driven molecular interactions. We suggest that nanoparticles alter weakly bound proteins by shifting the equilibrium towards the unfolded states at physiological temperature. We show that the classical approach based on nanoparticle separation from the biological medium fails to detect destabilization of weakly bound proteins, and therefore cannot be used to fully predict the biological effects of nanomaterials in situ.

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Section: Resultssupporting

confidence: 76%

Section: Snps Stabilize Partially Unfolded Conformationsmentioning

confidence: 99%

In Situ Analysis of Weakly Bound Proteins Reveals Molecular Basis of Soft Corona Formation

et al. 2020

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“…Regardless, this rate may be lowered again if a truly crowded environment with free floating proteins were used, as the excluded volume effect will come into play. 88 In line with this, some other studies have seen suppressed conformational dynamics due to crowding, 52,89,90 with the caveat that these studies did not examine a membrane crowded with neighboring membrane proteins.…”

mentioning

confidence: 99%

“…Environment effects on proteins are also poorly resolved. Proteins are capable of crowding together very effectively, and this crowding may stabilize protein structures; − however, this stabilization effect is dependent on the protein sequence and its shape, which is complicated by the fact that the protein shape itself can be modified by crowding. − However, there is substantial conflicting literature suggesting that protein crowding destabilizes proteins − or does not affect their stability at all, suggesting that whether the environment stabilizes or destabilizes a protein is due to its interactions with the environment ,,− from differences in enthalpic and entropic interactions. , Even examining a single protein of interest, some crowding agents can stabilize it while others destabilize it . Even less studied is how protein crowding affects the solvent environment.…”

mentioning

confidence: 99%

Glycosylation and Crowded Membrane Effects on Influenza Neuraminidase Stability and Dynamics

Seitz,

Deveci,

McCammon

2023

J. Phys. Chem. Lett.

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All protein simulations are conducted with varying degrees of simplification, oftentimes with unknown ramifications about how these simplifications affect the interpretability of the results. In this work, we investigated how protein glycosylation and lateral crowding effects modulate an array of properties characterizing the stability and dynamics of influenza neuraminidase. We constructed three systems: (1) glycosylated neuraminidase in a whole virion (i.e., crowded membrane) environment, (2) glycosylated neuraminidase in its own lipid bilayer, and (3) unglycosylated neuraminidase in its own lipid bilayer. We saw that glycans tend to stabilize the protein structure and reduce its conformational flexibility while restricting the solvent movement. Conversely, a crowded membrane environment encouraged exploration of the free energy landscape and a large-scale conformational change, while making the protein structure more compact. Understanding these effects informs what factors one must consider in attempting to recapture the desired level of physical accuracy.

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“…Proteins are capable of crowding together very effectively (30) and this crowding may stabilize protein structures (31)(32)(33)(34)(35)(36)(37) but this stabilization effect is dependent on the protein sequence and its shape (38) which is complicated by the fact that the protein shape itself can be modified by crowding. (39)(40)(41) However, there is substantial conflicting literature suggesting that protein crowding destabilizes proteins (42)(43)(44) or does not affect their stability at all, (45) suggesting that whether the environment stabilizes or destabilizes a protein is due to its interactions with the environment (42,43,(46)(47)(48)(49)(50)(51)(52) from differences in enthalpic and entropic interactions. (48,53) Even examining a single protein of interest, some crowding agents can stabilize it (54) while others destabilize it.…”

mentioning

confidence: 99%

Glycosylation and Crowded Membrane Effects on Influenza Neuraminidase Stability and Dynamics

Seitz,

Deveci,

McCammon

2023

Preprint

View full text Add to dashboard Cite

All protein simulations are conducted with varying degrees of simplifications, oftentimes with unknown ramifications on how these simplifications affect the interpretability of the results. In this work we investigated how protein glycosylation and lateral crowding effects modulate an array of properties characterizing the stability and dynamics of influenza neuraminidase. We constructed three systems: 1) Glycosylated neuraminidase in a whole virion (i.e. crowded membrane) environment 2) Glycosylated neuraminidase in its own lipid bilayer 3) Unglycosylated neuraminidase in its own lipid bilayer. We saw that glycans tend to stabilize the protein structure and reduce its conformational flexibility while restricting solvent movement. Conversely, a crowded membrane environment encouraged exploration of the free energy landscape and a large scale conformational change while making the protein structure more compact. Understanding these effects informs what factors one must consider while attempting to recapture the desired level of physical accuracy.

show abstract

Factors defining the effects of macromolecular crowding on dynamics and thermodynamic stability of heme proteins in-vitro

Cited by 9 publications

References 119 publications

In Situ Analysis of Weakly Bound Proteins Reveals Molecular Basis of Soft Corona Formation

In Situ Analysis of Weakly Bound Proteins Reveals Molecular Basis of Soft Corona Formation

Glycosylation and Crowded Membrane Effects on Influenza Neuraminidase Stability and Dynamics

Glycosylation and Crowded Membrane Effects on Influenza Neuraminidase Stability and Dynamics

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