Interactions of intrinsically disordered Thellungiella salsuginea dehydrins TsDHN-1 and TsDHN-2 with membranes — synergistic effects of lipid composition and temperature on secondary structure

2010 ◽  
Vol 88 (5) ◽  
pp. 791-807 ◽  
Author(s):  
Luna N. Rahman ◽  
Lin Chen ◽  
Sumaiya Nazim ◽  
Vladimir V. Bamm ◽  
Mahmoud W. Yaish ◽  
...  
Keyword(s):  
Secondary Structure ◽  
Synergistic Effects ◽  
Yukon Territory ◽  
Membrane Structures ◽  
Thellungiella Salsuginea ◽  
Intrinsically Disordered ◽  
Induced Folding ◽  
Large Unilamellar Vesicles ◽  
Unstructured Proteins ◽  
Extreme Cold

Dehydrins are intrinsically disordered (unstructured) proteins that are expressed in plants experiencing stressful conditions such as drought or low temperature. Dehydrins are typically found in the cytosol and nucleus, but also associate with chloroplasts, mitochondria, and the plasma membrane. Although their role is not completely understood, it has been suggested that they stabilize proteins or membrane structures during environmental stress, the latter association mediated by formation of amphipathic α-helices by conserved regions called the K-segments. Thellungiella salsuginea is a crucifer that thrives in the Canadian sub-Arctic (Yukon Territory) where it grows on saline-rich soils and experiences periods of both extreme cold and drought. We have cloned and expressed in Escherichia coli two dehydrins from this plant, denoted TsDHN-1 (acidic) and TsDHN-2 (basic). Here, we show using transmission-Fourier transform infrared (FTIR) spectroscopy that ordered secondary structure is induced and stabilized in these proteins by association with large unilamellar vesicles emulating the lipid compositions of plant plasma and organellar membranes. Moreover, this induced folding is enhanced at low temperatures, lending credence to the hypothesis that dehydrins stabilize plant outer and organellar membranes in conditions of cold.

Sequence Specificity Despite Intrinsic Disorder: How a Disease-Associated Val/Met Polymorphism Shifts Tertiary Interactions in a Long Disordered Protein

2019 ◽  
Author(s):  
Ruchi Lohia ◽  
Reza Salari ◽  
Grace Brannigan
Keyword(s):  
Secondary Structure ◽  
Electrostatic Interactions ◽  
Intrinsically Disordered Proteins ◽  
Disordered Proteins ◽  
Sequence Specificity ◽  
Intrinsically Disordered ◽  
Specific Effects ◽  
Heterogeneous Polymer ◽  
Non Local ◽  
Dynamics Simulations

<div>The role of electrostatic interactions and mutations that change charge states in intrinsically disordered proteins (IDPs) is well-established, but many disease-associated mutations in IDPs are charge-neutral. The Val66Met single nucleotide polymorphism (SNP) encodes a hydrophobic-to-hydrophobic mutation at the midpoint of the prodomain of precursor brain-derived neurotrophic factor (BDNF), one of the earliest SNPs to be associated with neuropsychiatric disorders, for which the underlying molecular mechanism is unknown. Here we report on over 250 μs of fully-atomistic, explicit solvent, temperature replica exchange molecular dynamics simulations of the 91 residue BDNF prodomain, for both the V66 and M66 sequence.</div><div>The simulations were able to correctly reproduce the location of both local and non-local secondary changes due to the Val66Met mutation when compared with NMR spectroscopy. We find that the local structure change is mediated via entropic and sequence specific effects. We show that the highly disordered prodomain can be meaningfully divided into domains based on sequence alone. Monte Carlo simulations of a self-excluding heterogeneous polymer, with monomers representing each domain, suggest the sequence would be effectively segmented by the long, highly disordered polyampholyte near the sequence midpoint. This is qualitatively consistent with observed interdomain contacts within the BDNF prodomain, although contacts between the two segments are enriched relative to the self-excluding polymer. The Val66Met mutation increases interactions across the boundary between the two segments, due in part to a specific Met-Met interaction with a Methionine in the other segment. This effect propagates to cause the non-local change in secondary structure around the second methionine, previously observed in NMR. The effect is not mediated simply via changes in inter-domain contacts but is also dependent on secondary structure formation around residue 66, indicating a mechanism for secondary structure coupling in disordered proteins. </div>

scholarly journals Drug and dye binding induced folding of the intrinsically disordered antimicrobial peptide CM15

RSC Advances ◽  
2017 ◽  
Vol 7 (65) ◽  
pp. 41091-41097 ◽  
Author(s):  
Ferenc Zsila ◽  
Szilvia Bősze ◽  
Kata Horváti ◽  
Imola Cs. Szigyártó ◽  
Tamás Beke-Somfai
Keyword(s):  
Antimicrobial Peptide ◽  
Conformational Transition ◽  
Drug Binding ◽  
Intrinsically Disordered ◽  
Induced Folding ◽  
Dye Binding ◽  
Natively Unfolded

Drug binding induces the disorder-to-order conformational transition of the natively unfolded antimicrobial peptide CM15.

scholarly journals WT and A53T α-synuclein systems: Melting Diagram and its new interpretation

2019 ◽  
Author(s):  
M. Bokor ◽  
Á. Tantos ◽  
P. Tompa ◽  
K.-H. Han ◽  
K. Tompa
Keyword(s):  
Secondary Structure ◽  
Structural Disorder ◽  
Water Molecules ◽  
Hydration Water ◽  
Wild Type ◽  
Water Binding ◽  
Potential Barriers ◽  
Intrinsically Disordered ◽  
Mobile Water ◽  
Binding Interfaces

AbstractParkinson’s disease is connected with abnormal α-synuclein (αS) aggregation. Energetics of potential barriers governing motions of hydration water is examined. Information about the distributions and heights of potential barriers is gained by a thermodynamical approach. The ratios of the heterogeneous water-binding interfaces measure proteins’ structural disorder. All αS forms possess secondary structural elements though they are intrinsically disordered. Monomers are functional at the lowest potential barriers, where mobile hydration water exists, with monolayer coverage of mobile hydration. The αS monomer contains 33% secondary structure and is more compact than a random coil. A53T αS monomer has a more open structure than the wild type. Monomers realize all possible hydrogen bonds. Half of the mobile hydration water amount for monomers is missing in αS oligomers and αS amyloids. Oligomers are ordered by 66%. Mobile water molecules in the first hydration shell of amyloids are the weakest bound compared to other forms. Wild type and A53T amyloids show identical, low-level hydration, and are considered as disordered to 75%.Statement of SignificanceAggregation of α-synuclein into oligomers, amyloid fibrils is a hallmark of Parkinson’s disease. A thermodynamic approach provides information on the heterogeneity of protein-water bonds in the wild type and A53T mutant monomers, oligomers, amyloids. This information can be related to ratios of heterogeneous water-binding interfaces, which measure the proteins’ structural disorder. Both α-synuclein monomers are intrinsically disordered. The monomers nevertheless have 33% secondary structure. They are functional as long as mobile water molecules surround them. They realize every possible H-bonds with water. Oligomers are like globular proteins with 66% ordered structure. Amyloids are disordered to 75% and are poorly hydrated with loosely bound water. Their hydration is identical. Oligomers, amyloids have only half as much hydrating mobile water as monomers.

scholarly journals Calcium-Induced Folding and Stabilization of the Intrinsically Disordered RTX Domain of the CyaA Toxin

2010 ◽  
Vol 99 (11) ◽  
pp. 3744-3753 ◽  
Author(s):  
Alexandre Chenal ◽  
Johanna C. Karst ◽  
Ana Cristina Sotomayor Pérez ◽  
Anna Katarzyna Wozniak ◽  
Bruno Baron ◽  
...  
Keyword(s):  
Intrinsically Disordered ◽  
Induced Folding

scholarly journals Random coil chemical shifts for serine, threonine and tyrosine phosphorylation over a broad pH range

2019 ◽  
Vol 73 (12) ◽  
pp. 713-725 ◽  
Author(s):  
Ruth Hendus-Altenburger ◽  
Catarina B. Fernandes ◽  
Katrine Bugge ◽  
Micha B. A. Kunze ◽  
Wouter Boomsma ◽  
...  
Keyword(s):  
Chemical Shift ◽  
Secondary Structure ◽  
Intrinsically Disordered Proteins ◽  
Chemical Shifts ◽  
Random Coil ◽  
Disordered Proteins ◽  
Phosphoryl Group ◽  
Intrinsically Disordered ◽  
Intrinsically Disordered Regions ◽  
Secondary Chemical

Abstract Phosphorylation is one of the main regulators of cellular signaling typically occurring in flexible parts of folded proteins and in intrinsically disordered regions. It can have distinct effects on the chemical environment as well as on the structural properties near the modification site. Secondary chemical shift analysis is the main NMR method for detection of transiently formed secondary structure in intrinsically disordered proteins (IDPs) and the reliability of the analysis depends on an appropriate choice of random coil model. Random coil chemical shifts and sequence correction factors were previously determined for an Ac-QQXQQ-NH2-peptide series with X being any of the 20 common amino acids. However, a matching dataset on the phosphorylated states has so far only been incompletely determined or determined only at a single pH value. Here we extend the database by the addition of the random coil chemical shifts of the phosphorylated states of serine, threonine and tyrosine measured over a range of pH values covering the pKas of the phosphates and at several temperatures (www.bio.ku.dk/sbinlab/randomcoil). The combined results allow for accurate random coil chemical shift determination of phosphorylated regions at any pH and temperature, minimizing systematic biases of the secondary chemical shifts. Comparison of chemical shifts using random coil sets with and without inclusion of the phosphoryl group, revealed under/over estimations of helicity of up to 33%. The expanded set of random coil values will improve the reliability in detection and quantification of transient secondary structure in phosphorylation-modified IDPs.

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