Conformation of poly-l-glutamate is independent of ionic strength

Xiong, Kan; Ma, Lu; Asher, Sanford A.

doi:10.1016/j.bpc.2011.11.002

Cited by 12 publications

(18 citation statements)

References 38 publications

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“…(48–50) We surprisingly find that DQ10 adopts 2.5 1 -helix conformations. The mechanism(s) by which these 2.5 1 -helix conformations of Q10 are stabilized is unknown.…”

Section: Resultsmentioning

confidence: 79%

UV Resonance Raman Spectroscopy Monitors Polyglutamine Backbone and Side Chain Hydrogen Bonding and Fibrillization

2012

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We utilize 198 and 204 nm excited UV resonance Raman spectroscopy (UVRR) and circular dichroism spectroscopy (CD) to monitor the backbone conformation and the GLN side chain hydrogen bonding (HB) of a short, mainly polyGLN peptide of sequence D2Q10K2 (Q10). We measured the UVRR spectra of valeramide to determine the dependence of the primary amide vibrations on amide HB. We observe that non-disaggregated Q10 (NDQ10) solution (prepared by directly dissolving the original synthesized peptide in pure water) occurs in a β-sheet conformation, where the GLN side chains form HB to either the backbone or other GLN side chains. At 60 °C, these solutions readily form amyloid fibrils. We used the polyGLN disaggregation protocol of Wetzel et al (Methods Enzymol, 2006, 413, 34–74) to dissolve the Q10 β-sheet aggregates. We observe that the disaggregated Q10 (DQ10) solutions adopt PPII-like and 2.51-helix conformations where the GLN side chains form HB to water. In contrast, these samples do not form fibrils. The NDQ10 β-sheet solution structure is essentially identical to that found in the NDQ10 solid formed upon solution evaporation. The DQ10 PPII and 2.51-helix solution structure is essentially identical to that in the DQ10 solid. Although the NDQ10 solution readily forms fibrils when heated, the DQ10 solution does not form fibrils unless seeded by NDQ10 solution. This result demonstrates very high activation barriers between these solution conformations. The NDQ10 fibril secondary structure is essentially identical to that of the NDQ10 solution, except that the NDQ10 fibril backbone conformational distribution is narrower than in the dissolved species. The NDQ10 fibril GLN side chain geometry is more constrained than when NDQ10 is in solution. The NDQ10 fibril structure is identical to that of the DQ10 fibril seeded by the NDQ10 solution.

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“…(48–50) We surprisingly find that DQ10 adopts 2.5 1 -helix conformations. The mechanism(s) by which these 2.5 1 -helix conformations of Q10 are stabilized is unknown.…”

Section: Resultsmentioning

confidence: 79%

UV Resonance Raman Spectroscopy Monitors Polyglutamine Backbone and Side Chain Hydrogen Bonding and Fibrillization

2012

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“…The horizontal axis represents fractions in systems with Na + counterions, and the vertical axis with K + . The dotted diagonal corresponds to the results that are independent of the counterion type; this independence is suggested by experimental observations for PGA in NaCl and KCl solutions [27]. We are not aware of similar experiments using PASA but similar behavior is assumed.…”

Section: Fractions Of Major Backbone Conformationsmentioning

confidence: 75%

“…In our previous paper we observed strong dependence on parameterization, but the data could not be used to determine which parameterization is the most accurate [14]. The results of our present work using both structural static and dynamic properties together with a comparison to experimental data [19][20][21][22][23][24][25][26][27] allows us to provide some recommendations. These recommendations could be used as a guideline for a simulations of anionic poly(amino acids).…”

Section: Introductionmentioning

confidence: 93%

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Changes in the Local Conformational States Caused by Simple Na+ and K+ Ions in Polyelectrolyte Simulations: Comparison of Seven Force Fields With and Without NBFIX and ECC Corrections

Lukasheva¹,

Tolmachev²,

Martinez‐Seara³

et al. 2021

Preprint

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Electrostatic interactions have a determining role in conformational and dynamic behavior of polyelectrolyte molecules [1]. In this study, anionic polyelectrolyte molecules, poly(glutamic acid) (PGA) and poly(aspartic acid) (PASA), in water solution with the most commonly used K+ or Na+ counterions were investigated using atomistic molecular dynamics (MD) simulations. Seven common force fields, AMBER99SB-ILDN, AMBER14SB, AMBER-FB15, CHARMM22*, CHARMM27, CHARMM36m and OPLS-AA/L, both with their native parameters and with the non-bonded fix (NBFIX) and electronic continuum corrections (ECC) to were studied. These corrections have bene introduced to correct for the problem of overbinding of ions to the charged groups of polyelectrolytes. Physical properties, such as molecular sizes, local structure and dynamics, were studied using two types of common counterions, potassium and sodium. The results show that in some cases, the macroion size and dynamics depend strongly on the models (parameters) for the counterions due to strong overbinding of ions and charged side chain groups. The local structures and dynamics are more sensitive on dihedral angle parameterization resulting in a preference for defined monomer conformations amd the type of correction used.

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“…Furthermore, we can calculate the Gibbs free energy landscape of the Ψ angle coordinate by applying the Boltzmann relation to the Ψ angle distribution [16,17]. This methodology has been extensively used to investigate the secondary structure of peptides and proteins [6,10,[18][19][20][21][22].…”

Section: Uvrr Peptide ψ Ramachandran Angle Markermentioning

confidence: 99%

Ultraviolet resonance Raman spectroscopic markers for protein structure and dynamics

Jakubek

Handen

White

et al. 2018

TrAC Trends in Analytical Chemistry

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UV resonance Raman (UVRR) spectroscopy is a powerful tool for investigating the structure of biological molecules, such as proteins. Numerous UVRR spectroscopic markers that provide information on the structure and environment of the protein backbone and of amino acid side chains have recently been discovered. Combining these UVRR markers with hydrogen-deuterium exchange and advanced statistics is a powerful tool for studying protein systems, including the structure and formation mechanism of protein aggregates and amyloid fibrils. These techniques allow crucial new insights into the structure and dynamics of proteins, such as polyglutamine peptides, which are associated with 10 different neurodegenerative diseases. Here we summarize the spectroscopic structural markers recently developed and the important insights they provide.

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Conformation of poly-l-glutamate is independent of ionic strength

Cited by 12 publications

References 38 publications

UV Resonance Raman Spectroscopy Monitors Polyglutamine Backbone and Side Chain Hydrogen Bonding and Fibrillization

UV Resonance Raman Spectroscopy Monitors Polyglutamine Backbone and Side Chain Hydrogen Bonding and Fibrillization

Changes in the Local Conformational States Caused by Simple Na+ and K+ Ions in Polyelectrolyte Simulations: Comparison of Seven Force Fields With and Without NBFIX and ECC Corrections

Ultraviolet resonance Raman spectroscopic markers for protein structure and dynamics

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