Post-translational S-Nitrosylation Is an Endogenous Factor Fine Tuning the Properties of Human S100A1 Protein

Živković, Martina Lenarčič; Zaręba-Kozioł, Monika; Zhukova, Liliya; Poznański, Jarosław; Zhukov, Igor; Wysłouch‐Cieszyńska, Aleksandra

doi:10.1074/jbc.m112.418392

Cited by 21 publications

(24 citation statements)

References 76 publications

(103 reference statements)

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“…More than 10 • angle differences in apo and holo states are depicted in bold and italic fonts. Angle calculations in the apo and holo states showed a vast increment, which was in strong agreement with the findings of previous studies [25,26]. Since the interhelical angles constantly increased, the standard deviation showed little fluctuations at the later stage of simulation (after 50 ns), as compared to the initial stage.…”

Section: Angle Estimations Between Helix-loop-helix Domainssupporting

confidence: 91%

“…Previously, genome and proteome level studies revealed specific Ca 2+ binding proteins and highlighted their importance with respect to medical relevance [42,43]. Earlier, nuclear magnetic resonance studies have exposed atomic-resolution details of the S100A1 conformations in the apo-S100A1 [25,44], holo-S100A1 [11,25], and target protein-bound states [13,45].…”

Section: Discussionmentioning

confidence: 99%

“…The S100A1 protein was simulated using the coordinates retrieved from the Protein Data Bank for the apo and holo states (PDB ID: 2LLU and 2LP3, respectively) [25,26]. Gromacs 4.6.7 suite of the package was employed to carry out MD simulations [27] with the 53a6 parameter set of the Gromos96 force field [28].…”

Section: System Buildingmentioning

confidence: 99%

See 2 more Smart Citations

Understanding Calcium-Dependent Conformational Changes in S100A1 Protein: A Combination of Molecular Dynamics and Gene Expression Study in Skeletal Muscle

Chaturvedi

Ahmad

Yadav

et al. 2020

Cells

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The S100A1 protein, involved in various physiological activities through the binding of calcium ions (Ca2+), participates in several protein-protein interaction (PPI) events after Ca2+-dependent activation. The present work investigates Ca2+-dependent conformational changes in the helix-EF hand-helix using the molecular dynamics (MD) simulation approach that facilitates the understanding of Ca2+-dependent structural and dynamic distinctions between the apo and holo forms of the protein. Furthermore, the process of ion binding by inserting Ca2+ into the bulk of the apo structure was simulated by molecular dynamics. Expectations of the simulation were demonstrated using cluster analysis and a variety of structural metrics, such as interhelical angle estimation, solvent accessible surface area, hydrogen bond analysis, and contact analysis. Ca2+ triggered a rise in the interhelical angles of S100A1 on the binding site and solvent accessible surface area. Significant configurational regulations were observed in the holo protein. The findings would contribute to understanding the molecular basis of the association of Ca2+ with the S100A1 protein, which may be an appropriate study to understand the Ca2+-mediated conformational changes in the protein target. In addition, we investigated the expression profile of S100A1 in myoblast differentiation and muscle regeneration. These data showed that S100A1 is expressed in skeletal muscles. However, the expression decreases with time during the process of myoblast differentiation.

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Section: Angle Estimations Between Helix-loop-helix Domainssupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Understanding Calcium-Dependent Conformational Changes in S100A1 Protein: A Combination of Molecular Dynamics and Gene Expression Study in Skeletal Muscle

Chaturvedi

Ahmad

Yadav

et al. 2020

Cells

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“…Total protein concentration of the lysate was adjusted to 1 mg/ml. Obtained cell lysates were treated using BST as previously described [ 37 , 44 ]. Supernatants from each BST step were collected, proteins were separated using 15% SDS–PAGE and transferred onto PVDF membrane (0.22 μm).…”

Section: Methodsmentioning

confidence: 99%

“…In our previous work we have revealed that Cys84 in recombinant S100B and Cys85 in another S100 protein family member, recombinant S100A1, are S-nitrosylated in a Ca 2+ - dependent manner by S-nitrosoglutathione (GSNO)—a low-molecular weight endogenous nitrosothiol [ 43 ]. Furthermore, we have reported that the Cys85 of S100A1 protein is an endogenous target of S-nitrosylation in PC12 cells [ 44 ]. Comparison of structural NMR data for unmodified S100A1SH and S100A1SNO found that the modified Cys85 thiol side chain is involved in a thiol/aromatic molecular switch which changes the conformation and Ca 2+ ion affinity of S100A1.…”

Section: Introductionmentioning

confidence: 99%

An Interplay of S-Nitrosylation and Metal Ion Binding for Astrocytic S100B Protein

et al. 2016

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Mammalian S100B protein plays multiple important roles in cellular brain processes. The protein is a clinically used marker for several pathologies including brain injury, neurodegeneration and cancer. High levels of S100B released by astrocytes in Down syndrome patients are responsible for reduced neurogenesis of neural progenitor cells and induction of cell death in neurons. Despite increasing understanding of S100B biology, there are still many questions concerning the detailed molecular mechanisms that determine specific activities of S100B. Elevated overexpression of S100B protein is often synchronized with increased nitric oxide-related activity. In this work we show S100B is a target of exogenous S-nitrosylation in rat brain protein lysate and identify endogenous S-nitrosylation of S100B in a cellular model of astrocytes. Biochemical studies are presented indicating S-nitrosylation tunes the conformation of S100B and modulates its Ca2+ and Zn2+ binding properties. Our in vitro results suggest that the possibility of endogenous S-nitrosylation should be taken into account in the further studies of in vivo S100B protein activity, especially under conditions of increased NO-related activity.

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Characterization of Pre‐Dissociative Structures of the E6AP Trimer by All‐atom Unbiased Molecular Dynamics

Chaturvedi

Nachliel

Gutman

2020

Israel Journal of Chemistry

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The activity of the E6AP protein, a member of the ubiquitin transfer system, is regulated through the association‐dissociation of its homo‐trimeric structure. Under physiologic conditions, this protein is in a mixture of mono, di and tri‐mere complexes, where the D543A mutation further destabilize the complex. These featured render this protein as an excellent model for a study of pre‐dissociation events that can be detected by applying a cluster analysis of the ∼200 ns long trajectories. The analysis of the WT complex revealed inherent divergence of the subunits, each exhibiting multiplicity of configurations that differ in their energy. Surprisingly, the trimer is more stable than the subunits. The D543A mutation caused the trimer complex to assume many equi‐potential configurations, rendering it more flexible than the subunits. The trimeric destabilization is not observed in a mutant that affects only the structure of the active site. We propose that the pre‐dissociation configurations can be identified much earlier than the structural disintegration of a proteinous complex.

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Post-translational S-Nitrosylation Is an Endogenous Factor Fine Tuning the Properties of Human S100A1 Protein

Cited by 21 publications

References 76 publications

Understanding Calcium-Dependent Conformational Changes in S100A1 Protein: A Combination of Molecular Dynamics and Gene Expression Study in Skeletal Muscle

Understanding Calcium-Dependent Conformational Changes in S100A1 Protein: A Combination of Molecular Dynamics and Gene Expression Study in Skeletal Muscle

An Interplay of S-Nitrosylation and Metal Ion Binding for Astrocytic S100B Protein

Characterization of Pre‐Dissociative Structures of the E6AP Trimer by All‐atom Unbiased Molecular Dynamics

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