Change search
Link to record
Permanent link

Direct link
Eremina, Nadejda
Alternative names
Publications (10 of 12) Show all publications
Marter, K., Wetzel, J., Eichhorst, J., Eremina, N., Leboulle, G., Barth, A., . . . Eisenhardt, D. (2017). Inhibition of Protein Synthesis with Highly Soluble Caged Compounds. ChemistrySelect, 2(22), 6212-6217
Open this publication in new window or tab >>Inhibition of Protein Synthesis with Highly Soluble Caged Compounds
Show others...
2017 (English)In: ChemistrySelect, ISSN 2365-6549, Vol. 2, no 22, p. 6212-6217Article in journal (Refereed) Published
Abstract [en]

To target protein synthesis in defined areas, e.g. neuropiles of small brains or subcellular structures, locally restricted inhibition of protein synthesis is needed and can be realized by caged compounds of protein synthesis inhibitors (PSI). Since organic solvents interfere with protein synthesis themselves, the use of water-soluble caged PSIs is a prerequisite in studies on protein synthesis. Such compounds are sparsely available. We developed and characterized efficient highly soluble caged compounds of the PSIs anisomycin and emetine masking their biological activity with a {8-[bis(carboxymethyl)aminomethyl]-6-bromo-7-hydroxycoumarin-4-yl}methoxycarbonyl (BBHCMOC) derivative. The absorption spectra of the resulting BBHCMOC-caged anisomycin and BBHCMOC-caged emetine show long-wavelength maxima and the extinction coefficients are high, allowing uncaging under non-damaging light conditions. When uncaged, these caged PSIs reliably inhibit protein synthesis in an in vitro translation system and in cell culture. Taken the whole spectrum of properties into account, our BBHCMOC-caged PSIs are highly qualified for in vivo studies.

Keywords
anisomycin, caged compounds, emetine, protein synthesis, protecting groups
National Category
Chemical Sciences
Identifiers
urn:nbn:se:su:diva-147158 (URN)10.1002/slct.201701175 (DOI)000407471900004 ()
Available from: 2017-09-22 Created: 2017-09-22 Last updated: 2022-02-28Bibliographically approved
Eriksson, S., Eremina, N., Barth, A., Danielsson, J. & Harryson, P. (2016). Membrane-Induced Folding of the Plant Stress Dehydrin Lti30. Plant Physiology, 171(2), 932-943
Open this publication in new window or tab >>Membrane-Induced Folding of the Plant Stress Dehydrin Lti30
Show others...
2016 (English)In: Plant Physiology, ISSN 0032-0889, E-ISSN 1532-2548, Vol. 171, no 2, p. 932-943Article in journal (Refereed) Published
Abstract [en]

Dehydrins are disordered proteins that are expressed in plants as a response to embryogenesis and water-related stress. The molecular function and structural action of the dehydrins are yet elusive, but increasing evidence points to a role in protecting the structure and functional dynamics of cell membranes. An intriguing example is the cold-induced dehydrin Lti30 that binds to membranes by its conserved K segments. Moreover, this binding can be regulated by pH and phosphorylation and shifts the membrane phase transition to lower temperatures, consistent with the protein's postulated function in cold stress. In this study, we reveal how the Lti30-membrane interplay works structurally at atomic level resolution in Arabidopsis (Arabidopsis thaliana). Nuclear magnetic resonance analysis suggests that negatively charged lipid head groups electrostatically capture the protein's disordered K segments, which locally fold up into a-helical segments on the membrane surface. Thus, Lti30 conforms to the general theme of structure-function relationships by folding upon binding, in spite of its disordered, atypically hydrophilic and repetitive sequence signatures. Moreover, the fixed and well-defined structure of the membrane-bound K segments suggests that dehydrins have the molecular prerequisites for higher level binding specificity and regulation, raising new questions about the complexity of their biological function.

National Category
Biological Sciences
Research subject
Biochemistry
Identifiers
urn:nbn:se:su:diva-133244 (URN)10.1104/pp.15.01531 (DOI)000380699200015 ()27208263 (PubMedID)
Available from: 2016-09-07 Created: 2016-09-05 Last updated: 2022-02-23Bibliographically approved
Baldassarre, M., Li, C., Eremina, N., Goormaghtigh, E. & Barth, A. (2015). Simultaneous Fitting of Absorption Spectra and Their Second Derivatives for an Improved Analysis of Protein Infrared Spectra. Molecules, 20(7), 12599-12622
Open this publication in new window or tab >>Simultaneous Fitting of Absorption Spectra and Their Second Derivatives for an Improved Analysis of Protein Infrared Spectra
Show others...
2015 (English)In: Molecules, ISSN 1431-5157, E-ISSN 1420-3049, Vol. 20, no 7, p. 12599-12622Article in journal (Refereed) Published
Abstract [en]

Infrared spectroscopy is a powerful tool in protein science due to its sensitivity to changes in secondary structure or conformation. In order to take advantage of the full power of infrared spectroscopy in structural studies of proteins, complex band contours, such as the amide I band, have to be decomposed into their main component bands, a process referred to as curve fitting. In this paper, we report on an improved curve fitting approach in which absorption spectra and second derivative spectra are fitted simultaneously. Our approach, which we name co-fitting, leads to a more reliable modelling of the experimental data because it uses more spectral information than the standard approach of fitting only the absorption spectrum. It also avoids that the fitting routine becomes trapped in local minima. We have tested the proposed approach using infrared absorption spectra of three mixed α/β proteins with different degrees of spectral overlap in the amide I region: ribonuclease A, pyruvate kinase, and aconitase.

Keywords
Amide I, Curve fitting, Fourier-transform infrared spectroscopy, FT-IR, Second derivative, Secondary structure
National Category
Physical Chemistry
Research subject
Biochemistry
Identifiers
urn:nbn:se:su:diva-122481 (URN)10.3390/molecules200712599 (DOI)000368695400060 ()26184143 (PubMedID)
Available from: 2015-11-03 Created: 2015-11-03 Last updated: 2023-08-28Bibliographically approved
Morgunova, E., Yin, Y., Jolma, A., Dave, K., Schmierer, B., Popov, A., . . . Taipale, J. (2015). Structural insights into the DNA-binding specificity of E2F family transcription factors. Nature Communications, 6, Article ID 10050.
Open this publication in new window or tab >>Structural insights into the DNA-binding specificity of E2F family transcription factors
Show others...
2015 (English)In: Nature Communications, E-ISSN 2041-1723, Vol. 6, article id 10050Article in journal (Refereed) Published
Abstract [en]

The mammalian cell cycle is controlled by the E2F family of transcription factors. Typical E2Fs bind to DNA as heterodimers with the related dimerization partner (DP) proteins, whereas the atypical E2Fs, E2F7 and E2F8 contain two DNA-binding domains (DBDs) and act as repressors. To understand the mechanism of repression, we have resolved the structure of E2F8 in complex with DNA at atomic resolution. We find that the first and second DBDs of E2F8 resemble the DBDs of typical E2F and DP proteins, respectively. Using molecular dynamics simulations, biochemical affinity measurements and chromatin immunoprecipitation, we further show that both atypical and typical E2Fs bind to similar DNA sequences in vitro and in vivo. Our results represent the first crystal structure of an E2F protein with two DBDs, and reveal the mechanism by which atypical E2Fs can repress canonical E2F target genes and exert their negative influence on cell cycle progression.

National Category
Biological Sciences
Identifiers
urn:nbn:se:su:diva-126407 (URN)10.1038/ncomms10050 (DOI)000367568200003 ()26632596 (PubMedID)
Available from: 2016-02-08 Created: 2016-02-01 Last updated: 2023-03-28Bibliographically approved
Eremina, N. (2014). Infrared spectroscopic studies: from small molecules to large. (Doctoral dissertation). Stockholm: Department of Biochemistry and Biophysics, Stockholm University
Open this publication in new window or tab >>Infrared spectroscopic studies: from small molecules to large
2014 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Infrared light (IR) was first discovered by Friedrich Wilhelm Herschel in 1800. However, until 1940’s, molecular IR studies involved only water and small organic molecules, because of the long measurement times. Development Fourier transform infrared spectroscopy (FTIR) has minimized the time required to obtain data, making it possible to investigate bigger biological systems, e.g. proteins and nucleic acids.This thesis concentrates on the applications of different IR spectroscopic techniques to a variety of biological systems and development of new approaches to study complicated biological events.

The first paper in this work concerns using so-called caged compounds to study the aggregation of Alzheimer’s Aβ-peptide which is linked to the formation of neurotoxic fibrils in the brain. By adding caged-sulfate to the Aβ samples we were able to change the pH of the sample, while recording IR data and study fibril formation in a time-resolved manner. Then we used caged–ADP to study the production of ATP and creatine, mediated by creatine kinase (CK). Using CK as a helper enzyme we studied the effects of the phosphate binding on the secondary structure of SR Ca2+ATPse and determined the structural differences between two similar states Ca2E1ADP and Ca2E1ATP.

In the second part of the thesis we used ATR-FTIR spectroscopy and a specially designed dialysis setup, to develop a general method to detect ligand binding events by observing the IR absorbance changes in the water hydration shell around the molecules. The same method was used to determine the binding of DNA to the transcription factors of the E2F family. E2F proteins play main part in the gene regulatory networks that control cell development. However how they recognize their DNA-binding sites and the mechanism of binding is not well understood. By using ATR-FTIR, we observed the changes in the secondary structure of the proteins, as well as the distortions to the DNA upon E2F-DNA complex formation.

Place, publisher, year, edition, pages
Stockholm: Department of Biochemistry and Biophysics, Stockholm University, 2014. p. 59
Keywords
Infrared spectroscopy, transcription factors, DNA, creatine kinase, CaATPase, water, ligand binding
National Category
Biophysics
Research subject
Biopharmaceutics
Identifiers
urn:nbn:se:su:diva-101077 (URN)978-91-7447-876-1 (ISBN)
Public defence
2014-03-28, Magnélisalen, Kemiska övningslaboratoriet, Svante Arrhenius väg 16 B, Stockholm, 10:00 (English)
Opponent
Supervisors
Note

At the time of the doctoral defense, the following paper was unpublished and had a status as follows: Paper 4: Manuscript.

Available from: 2014-03-06 Created: 2014-02-24 Last updated: 2022-02-17Bibliographically approved
Eremina, N. & Barth, A. (2013). Use of Creatine Kinase To Induce Multistep Reactions in Infrared Spectroscopic Experiments. Journal of Physical Chemistry B, 117(48), 14967-14972
Open this publication in new window or tab >>Use of Creatine Kinase To Induce Multistep Reactions in Infrared Spectroscopic Experiments
2013 (English)In: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 117, no 48, p. 14967-14972Article in journal (Refereed) Published
Abstract [en]

An extension of current approaches to trigger enzymatic reactions in reaction-induced infrared difference spectroscopy experiments is described. A common procedure is to add a compound that induces a reaction in the protein of interest. To be able to induce multistep reactions, we explored here the use of creatine kinase (CK) for the study of phosphate transfer mechanisms. The enzymatic reaction of CK could be followed using bands at 1614 and 979 cm(-1) for creatine phosphate consumption, at 944 cm(-1) for ADP consumption, and at 1243, 992, and 917 cm(-1) for ATP formation. The potential of CK to induce multistep reactions in infrared spectroscopic experiments was demonstrated using the sarcoplasmic reticulum Ca2+-ATPase (SERCA1a) as the protein of interest. ADP binding to the ATPase was triggered by photolytic release of ADP from P-3-1-(2-nitro)phenylethyl ADP (caged ADP). CK added in small amounts converted the released ADP to ATP on the time scale of minutes. This phosphorylated the ATPase and led to the formation of the first phosphoenzyme intermediate Ca(2)E1P. Thus a difference spectrum could be obtained that reflected the reaction from the ADP ATPase complex to the first phosphoenzyme intermediate. Comparison with a phosphorylation spectrum obtained when the initial state was the ATP ATPase complex revealed the contribution of ATP's gamma-phosphate to the conformational change of the ATPase upon nucleotide binding: gamma-phosphate binding modifies the structure of a beta-sheet, likely in the phosphorylation domain, and shifts its spectral position from similar to 1640 to similar to 1630 cm(-1). Upon phosphorylation of the ATPase, the beta-sheet relaxes back to a structure that is intermediate between that adopted in the ADP bound state and that in the ATP bound state.

Place, publisher, year, edition, pages
American Chemical Society (ACS), 2013
National Category
Physical Chemistry
Identifiers
urn:nbn:se:su:diva-98722 (URN)10.1021/jp409599p (DOI)000328101100009 ()
Funder
Knut and Alice Wallenberg FoundationSwedish Research Council
Note

AuthorCount:2;

Available from: 2014-01-09 Created: 2014-01-09 Last updated: 2022-02-24Bibliographically approved
Schaal, J., Dekowski, B., Wiesner, B., Eichhorst, J., Marter, K., Vargas, C., . . . Hagen, V. (2012). Coumarin-based octopamine phototriggers and their effects on an insect octopamine receptor. ChemBioChem (Print), 13(10), 1458-1464
Open this publication in new window or tab >>Coumarin-based octopamine phototriggers and their effects on an insect octopamine receptor
Show others...
2012 (English)In: ChemBioChem (Print), ISSN 1439-4227, E-ISSN 1439-7633, Vol. 13, no 10, p. 1458-1464Article in journal (Refereed) Published
Abstract [en]

We have developed and characterized efficient caged compounds of the neurotransmitter octopamine. For derivatization, we introduced [6-bromo-8-(diethylaminomethyl)-7-hydroxycoumarin-4-yl]methoxycarbonyl (DBHCMOC) and {6-bromo-7-hydroxy-8-[(piperazin-1-yl)methyl]coumarin-4-yl}methoxycarbonyl (PBHCMOC) moieties as novel photo-removable protecting groups. The caged compounds were functionally inactive when applied to heterologously expressed octopamine receptors (AmOctα1R). Upon irradiation with UV–visible or IR light, bioactive octopamine was released and evoked Ca2+ signals in AmOctα1R-expressing cells. The pronounced water solubility of compounds 24 in particular holds great promise for these substances as excellent phototriggers of this important neurotransmitter.

Keywords
caged compounds, coumarins, neurotransmitters, photolysis, protecting groups
National Category
Biological Sciences
Research subject
Biophysics; Biochemistry
Identifiers
urn:nbn:se:su:diva-75962 (URN)10.1002/cbic.201200110 (DOI)000305941900013 ()
Available from: 2012-05-07 Created: 2012-05-07 Last updated: 2022-02-24Bibliographically approved
Kumar, S., Eremina, N. & Barth, A. (2012). Detection of Ligand Binding to Proteins through Observation of Hydration Water. Journal of Physical Chemistry B, 116(48), 13968-13974
Open this publication in new window or tab >>Detection of Ligand Binding to Proteins through Observation of Hydration Water
2012 (English)In: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 116, no 48, p. 13968-13974Article in journal (Refereed) Published
Abstract [en]

Drug development is impeded by the need to design for each drug target a test that detects the binding of drug candidate molecules to the target protein. Therefore, a general method to detect ligand binding is highly desirable. Here, we present an observation toward developing such a method, which is based on monitoring a change in water absorption by infrared spectroscopy. Infrared spectroscopy has high sensitivity for water, and changes in its hydrogen bond pattern can be observed. We studied absorption changes of water upon the addition of phosphenolpyruvate or Mg2+ to pyruvate kinase. In each case, there is a decrease in the absorption of water in the 3000-3100 cm(-1) region on the low wavenumber side of the OH stretching vibration when a ligand binds to the protein. Our results suggest that the weaker water absorption is due to the release of protein-bound water into bulk water during ligand binding. This observation has high potential for drug development as well as for basic research because it can lead to a general method for detecting molecular association events that (i) is label-free, (ii) works with both binding partners being in aqueous solution, and (iii) is based on a universal process that takes place in all binding events.

National Category
Biological Sciences
Identifiers
urn:nbn:se:su:diva-84809 (URN)10.1021/jp307560r (DOI)000311921700003 ()
Note

AuthorCount:3;

Available from: 2013-01-02 Created: 2013-01-02 Last updated: 2022-02-24Bibliographically approved
Mandal, P., Eremina, N. & Barth, A. (2012). Formation of Two Different Types of Oligomers in the Early Phase of pH-Induced Aggregation of the Alzheimer A beta(12-28) Peptide. Journal of Physical Chemistry B, 116(41), 12389-12397
Open this publication in new window or tab >>Formation of Two Different Types of Oligomers in the Early Phase of pH-Induced Aggregation of the Alzheimer A beta(12-28) Peptide
2012 (English)In: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 116, no 41, p. 12389-12397Article in journal (Refereed) Published
Abstract [en]

The early phase in the aggregation process of the Alzheimer's peptide A beta(12-28) with both protected and unprotected ends was studied by time-resolved infrared spectroscopy and circular dichroism spectroscopy. Aggregation in the time-resolved experiments was initiated by a rapid pH drop caused by the photolysis of 1-(2-nitrophenyl)ethyl sulfate (caged sulfate). The infrared spectra indicate two different types of aggregates from both versions of the A beta(12-28) peptide. One type has small and/or twisted beta sheets with a beta-sheet band at 1627 cm(-1), They form fast (within 60 ms), presumably from initial aggregates, and their spectral signature is consistent with a beta-barrel structure. The other type arises relatively slowly from unstructured monomers on the seconds-to-minutes time scale and forms at lower pH than the first type. These beta sheets are antiparallel, planar, and large and show an absorption band at 1622 cm(-1) that shifts to 1617 cm(-1) in 12 min with most of the shift occurring in 10 s.

National Category
Physical Chemistry
Identifiers
urn:nbn:se:su:diva-83008 (URN)10.1021/jp305015g (DOI)000309902400002 ()
Note

AuthorCount:3;

Available from: 2012-12-05 Created: 2012-12-03 Last updated: 2022-02-24Bibliographically approved
Eremina, N. (2012). Infrared spectroscopic studies of biological processes. (Licentiate dissertation). Stockholm: Stockholm University
Open this publication in new window or tab >>Infrared spectroscopic studies of biological processes
2012 (English)Licentiate thesis, monograph (Other academic)
Place, publisher, year, edition, pages
Stockholm: Stockholm University, 2012. p. 67
National Category
Biological Sciences
Identifiers
urn:nbn:se:su:diva-83060 (URN)
Available from: 2013-01-09 Created: 2012-12-03 Last updated: 2022-02-17Bibliographically approved
Organisations

Search in DiVA

Show all publications