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Karlsson, Björn C. G., DocentORCID iD iconorcid.org/0000-0002-7392-0591
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Publications (10 of 65) Show all publications
Näsström, T., Dahlberg, T., Malyshev, D., Ådén, J., Andersson, P.-O., Andersson, M. & Karlsson, B. C. G. (2021). Synthetic NAC 71-82 Peptides Designed to Produce Fibrils with Different Protofilament Interface Contacts. International Journal of Molecular Sciences, 22(17), Article ID 9334.
Open this publication in new window or tab >>Synthetic NAC 71-82 Peptides Designed to Produce Fibrils with Different Protofilament Interface Contacts
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2021 (English)In: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 22, no 17, article id 9334Article in journal (Refereed) Published
Abstract [en]

Alpha-synucleinopathies are featured by fibrillar inclusions in brain cells. Although α-synuclein fibrils display structural diversity, the origin of this diversity is not fully understood. We used molecular dynamics simulations to design synthetic peptides, based on the NAC 71-82 amino acid fragment of α-synuclein, that govern protofilament contacts and generation of twisted fibrillar polymorphs. Four peptides with structures based on either single or double fragments and capped or non-capped ends were selected for further analysis. We determined the fibrillar yield and the structures from these peptides found in the solution after fibrillisation using protein concentration determination assay and circular dichroism spectroscopy. In addition, we characterised secondary structures formed by individual fibrillar complexes using laser-tweezers Raman spectroscopy. Results suggest less mature fibrils, based on the lower relative β-sheet content for double- than single-fragment peptide fibrils. We confirmed this structural difference by TEM analysis which revealed, in addition to short protofibrils, more elongated, twisted and rod-like fibril structures in non-capped and capped double-fragment peptide systems, respectively. Finally, time-correlated single-photon counting demonstrated a difference in the Thioflavin T fluorescence lifetime profiles upon fibril binding. It could be proposed that this difference originated from morphological differences in the fibril samples. Altogether, these results highlight the potential of using peptide models for the generation of fibrils that share morphological features relevant for disease, e.g., twisted and rod-like polymorphs.

Place, publisher, year, edition, pages
MDPI, 2021
Keywords
alpha-synuclein; NAC 71-82; peptides; fibril polymorphs
National Category
Biochemistry and Molecular Biology Biophysics
Research subject
Chemistry, Biochemistry
Identifiers
urn:nbn:se:lnu:diva-106643 (URN)10.3390/ijms22179334 (DOI)000694357900001 ()34502242 (PubMedID)2-s2.0-85113788315 (Scopus ID)2021 (Local ID)2021 (Archive number)2021 (OAI)
Available from: 2021-08-30 Created: 2021-08-30 Last updated: 2023-01-18Bibliographically approved
Näsström, T., Ådén, J., Shibata, F., Andersson, P.-O. & Karlsson, B. C. G. (2020). A Capped Peptide of the Aggregation Prone NAC 71–82 Amino Acid Stretch of α-Synuclein Folds into Soluble β-Sheet Oligomers at Low and Elevated Peptide Concentrations. International Journal of Molecular Sciences, 21(5), 1-14, Article ID 1629.
Open this publication in new window or tab >>A Capped Peptide of the Aggregation Prone NAC 71–82 Amino Acid Stretch of α-Synuclein Folds into Soluble β-Sheet Oligomers at Low and Elevated Peptide Concentrations
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2020 (English)In: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 21, no 5, p. 1-14, article id 1629Article in journal (Refereed) Published
Abstract [en]

Although Lewy bodies and Lewy neurites are hallmarks of Parkinson's disease (PD) and dementia with Lewy bodies (DLB), misfolded α-synuclein oligomers are nowadays believed to be key for the development of these diseases. Attempts to target soluble misfolded species of the full-length protein have been limited so far, probably due to the fast aggregation kinetics and burial of aggregation prone segments in final cross-β-sheet fibrils. A previous characterisation study of fibrils prepared from a capped peptide of the non-amyloid β-component (NAC) 71-82 amino acid stretch of α-synuclein demonstrated an increased aggregation propensity resulting in a cross-β-structure that is also found in prion proteins. From this, it was suggested that capped NAC 71-82 peptide oligomers would provide interesting motifs with a capacity to regulate disease development. Here, we demonstrated, from a series of circular dichroism spectroscopic measurements and molecular dynamics simulations, the molecular-environment-sensitive behaviour of the capped NAC 71-82 peptide in a solution phase and the formation of β-sheet oligomeric structures in the supernatant of a fibrillisation mixture. These results highlighted the use of the capped NAC 71-82 peptide as a motif in the preparation of oligomeric β-sheet structures that potentially could be used in therapeutic strategies in the fight against progressive neurodegenerative disorders, such as PD and DLB.

Place, publisher, year, edition, pages
Basel, Switzerland: MDPI, 2020
Keywords
capped NAC 71–82 peptide, circular dichroism spectroscopy, molecular dynamics simulations, soluble β-sheet oligomers, Thioflavin T fluorescence, α-synuclein
National Category
Biochemistry and Molecular Biology
Research subject
Chemistry, Biochemistry
Identifiers
urn:nbn:se:lnu:diva-92696 (URN)10.3390/ijms21051629 (DOI)000524908500080 ()32120928 (PubMedID)2-s2.0-85080874648 (Scopus ID)
Funder
The Dementia Association - The National Association for the Rights of the Demented
Available from: 2020-03-05 Created: 2020-03-05 Last updated: 2023-01-18Bibliographically approved
Näsström, T., Andersson, P.-O., Lejon, C. & Karlsson, B. C. G. (2019). Amyloid fibrils prepared using an acetylated and methyl amidated peptide model of the alpha-Synuclein NAC 71-82 amino acid stretch contain an additional cross-beta structure also found in prion proteins. Scientific Reports, 9, 1-14, Article ID 15949.
Open this publication in new window or tab >>Amyloid fibrils prepared using an acetylated and methyl amidated peptide model of the alpha-Synuclein NAC 71-82 amino acid stretch contain an additional cross-beta structure also found in prion proteins
2019 (English)In: Scientific Reports, E-ISSN 2045-2322, Vol. 9, p. 1-14, article id 15949Article in journal (Refereed) Published
Abstract [en]

The 71-82 fragment of the non-amyloid-beta component (NAC) region of the Parkinson's disease (PD) and dementia with Lewy bodies (DLB) related protein alpha-Synuclein, has been reported to be important during protein misfolding. Although reports have demonstrated the importance of this fragment for the aggregation properties of the full-length protein, its exact role in pre-fibrillar oligomerisation, fibrillar growth and morphology has not yet been fully elucidated. Here, we provide evidence that fibrils prepared from an acetylated and methyl amidated peptide of the NAC 71-82 amino acid stretch of alpha-Synuclein are amyloid and contain, in addition to the cross-beta structure detected in the full-length protein fibrils, a cross-beta structure previously observed in prion proteins. These results shed light on the aggregation propensity of the NAC 71-82 amino acid stretch of the full-length protein but also the roles of the N- and C-terminal domains of alpha-Synuclein in balancing this aggregation propensity. The results also suggest that early aggregated forms of the capped NAC 71-82 peptide generated structures were stabilised by an anti-parallel and twisted beta-sheet motif. Due to its expected toxicity, this beta-sheet motif may be a promising molecular target for the development of therapeutic strategies for PD and DLB.

Place, publisher, year, edition, pages
Nature Publishing Group, 2019
National Category
Biochemistry and Molecular Biology
Research subject
Chemistry, Biochemistry
Identifiers
urn:nbn:se:lnu:diva-90198 (URN)10.1038/s41598-019-52206-5 (DOI)000493898100057 ()31685848 (PubMedID)2-s2.0-85074357322 (Scopus ID)
Available from: 2019-11-21 Created: 2019-11-21 Last updated: 2023-01-18Bibliographically approved
Steinz, M. M., Persson, M., Aresh, B., Olsson, K., Cheng, A. J., Ahlstrand, E., . . . Lanner, J. T. (2019). Oxidative hotspots on actin promote skeletal muscle weakness in rheumatoid arthritis. JCI Insight, 4(9), 1-16, Article ID e126347.
Open this publication in new window or tab >>Oxidative hotspots on actin promote skeletal muscle weakness in rheumatoid arthritis
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2019 (English)In: JCI Insight, ISSN 2324-7703, Vol. 4, no 9, p. 1-16, article id e126347Article in journal (Refereed) Published
Abstract [en]

Skeletal muscle weakness in patients suffering from rheumatoid arthritis (RA) adds to their impaired working abilities and reduced quality of life. However, little molecular insight is available on muscle weakness associated with RA. Oxidative stress has been implicated in the disease pathogenesis of RA. Here we show that oxidative post-translational modifications of the contractile machinery targeted to actin result in impaired actin polymerization and reduced force production. Using mass spectrometry, we identified the actin residues targeted by oxidative 3-nitrotyrosine (3-NT) or malondialdehyde adduct (MDA) modifications in weakened skeletal muscle from mice with arthritis and patients afflicted by RA. The residues were primarily located to three distinct regions positioned at matching surface areas of the skeletal muscle actin molecule from arthritis mice and RA patients. Moreover, molecular dynamic simulations revealed that these areas, here coined “hotspots”, are important for the stability of the actin molecule and its capacity to generate filaments and interact with myosin. Together, these data demonstrate how oxidative modifications on actin promote muscle weakness in RA patients and provide novel leads for targeted therapeutic treatment to improve muscle function.

Place, publisher, year, edition, pages
American Society for Clinical Investigation, 2019
National Category
Physiology
Research subject
Natural Science, Biomedical Sciences
Identifiers
urn:nbn:se:lnu:diva-82024 (URN)10.1172/jci.insight.126347 (DOI)000466814100015 ()2-s2.0-85070659458 (Scopus ID)
Available from: 2019-04-18 Created: 2019-04-18 Last updated: 2023-01-18Bibliographically approved
Nicholls, I. A., Olsson, G. D., Karlsson, B. C. G., Suriyanarayanan, S. & Wiklander, J. G. (2018). Theoretical and Computational Strategies in Molecularly Imprinted Polymer Development. In: Wlodzimierz Kutner, Piyush Sindhu Sharma (Ed.), Molecularly Imprinted Polymers for Analytical Chemistry Applications: (pp. 197-226). London: Royal Society of Chemistry
Open this publication in new window or tab >>Theoretical and Computational Strategies in Molecularly Imprinted Polymer Development
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2018 (English)In: Molecularly Imprinted Polymers for Analytical Chemistry Applications / [ed] Wlodzimierz Kutner, Piyush Sindhu Sharma, London: Royal Society of Chemistry, 2018, p. 197-226Chapter in book (Refereed)
Abstract [en]

Theoretical and computational studies of molecular imprinting have helped provide valuable insights concerning the nature of the molecular-level events underlying the recognition characteristics of molecularly imprinted materials. Here, we first present an overview of a thermodynamic treatment of factors governing the behaviour of these functional materials, and then a summary of the development and current status of the use of computational strategies for studying aspects of molecular imprinting and the resulting material properties.

Place, publisher, year, edition, pages
London: Royal Society of Chemistry, 2018
Series
Polymer Chemistry Series
National Category
Theoretical Chemistry
Research subject
Chemistry, Organic Chemistry
Identifiers
urn:nbn:se:lnu:diva-81879 (URN)10.1039/9781788010474-00197 (DOI)2-s2.0-85047140306 (Scopus ID)978-1-78262-647-3 (ISBN)978-1-78801-047-4 (ISBN)978-1-78801-427-4 (ISBN)
Available from: 2019-04-12 Created: 2019-04-12 Last updated: 2022-06-07Bibliographically approved
Karlsson, B. C. G. & Friedman, R. (2017). Dilution of whisky - the molecular perspective. Scientific Reports, 7(6489)
Open this publication in new window or tab >>Dilution of whisky - the molecular perspective
2017 (English)In: Scientific Reports, E-ISSN 2045-2322, Vol. 7, no 6489Article in journal (Refereed) Published
Abstract [en]

Whisky is distilled to around 70% alcohol by volume (vol-%) then diluted to about 40 vol-%, and often drunk after further slight dilution to enhance its taste. The taste of whisky is primarily associated with amphipathic molecules, such as guaiacol, but why and how dilution enhances the taste is not well understood. We carried out computer simulations of water-ethanol mixtures in the presence of guaiacol, providing atomistic details on the structure of the liquid mixture. We found that guaiacol is preferentially associated with ethanol, and, therefore, primarily found at the liquid-air interface in mixtures that contain up to 45 vol-% of ethanol. At ethanol concentrations of 59 vol-% or higher, guaiacol is increasingly surrounded by ethanol molecules and is driven to the bulk. This indicates that the taste of guaiacol in the whisky would be enhanced upon dilution prior to bottling. Our findings may apply to other flavour-giving amphipathic molecules and could contribute to optimising the production of spirits for desired tastes. Furthermore, it sheds light on the molecular structure of water-alcohol mixtures that contain small solutes, and reveals that interactions with the water may be negligible already at 89 vol-% of ethanol.

Place, publisher, year, edition, pages
Nature Publishing Group, 2017
Keywords
Whisky, dilution, guaiacol
National Category
Physical Chemistry Theoretical Chemistry
Research subject
Chemistry, Biochemistry; Chemistry, Organic Chemistry; Chemistry, Physical Chemistry
Identifiers
urn:nbn:se:lnu:diva-67349 (URN)10.1038/s41598-017-06423-5 (DOI)000407863100001 ()2-s2.0-85027838994 (Scopus ID)
Funder
Swedish National Infrastructure for Computing (SNIC), SNIC/2014-1-404 SNIC/2015-1-444
Note

Correction published in: Scientific Reports, 2018, vol 8, Article number 16448. DOI: 10.1038/s41598-018-34169-1

Available from: 2017-08-22 Created: 2017-08-22 Last updated: 2022-09-15Bibliographically approved
Shoravi, S., Olsson, G. D., Karlsson, B. C. G., Bexborn, F., Abghoui, Y., Hussain, J., . . . Nicholls, I. A. (2016). In silico screening of molecular imprinting prepolymerization systems: oseltamivir selective polymers through full-system molecular dynamics-based studies. Organic and biomolecular chemistry, 14(18), 4210-4219
Open this publication in new window or tab >>In silico screening of molecular imprinting prepolymerization systems: oseltamivir selective polymers through full-system molecular dynamics-based studies
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2016 (English)In: Organic and biomolecular chemistry, ISSN 1477-0520, E-ISSN 1477-0539, Vol. 14, no 18, p. 4210-4219Article in journal (Refereed) Published
Abstract [en]

All-component molecular dynamics studies were used to probe a library of oseltamivir molecularly imprinted polymer prepolymerization mixtures. Polymers included one of five functional monomers (acrylamide, hydroxyethylmethacrylate, methacrylic acid, 2-(triflouromethyl)acrylic acid, 4-vinylpyridine) and one of three porogens (acetonitrile, chloroform, methanol) combined with the crosslinking agent ethylene glycol dimethacrylate and initiator 2,2'-azobis(2-methylpropionitrile). Polymers were characterized by nitrogen gas sorption measurements and SEM, and affinity studies performed using radioligand binding in various media. In agreement with the predictions made from the simulations, polymers prepared in acetonitrile using either methacrylic or trifluoromethacrylic acid demonstrated the highest affinities for oseltamivir. Further, the ensemble of interactions observed in the methanol system provided an explanation for the morphology of polymers prepared in this solvent. The materials developed here offer potential for use in solid-phase extraction or for catalysis. The results illustrate the strength of this in silico strategy as a potential prognostic tool in molecularly imprinted polymer design.

National Category
Organic Chemistry
Research subject
Chemistry, Organic Chemistry
Identifiers
urn:nbn:se:lnu:diva-53319 (URN)10.1039/c6ob00305b (DOI)000375610600007 ()2-s2.0-84967333692 (Scopus ID)
Available from: 2016-06-10 Created: 2016-06-10 Last updated: 2022-03-16Bibliographically approved
Samyn, D. R., Van der Veken, J., Van Zeebroeck, G., Persson, B. L. & Karlsson, B. C. G. (2016). Key Residues and Phosphate Release Routes in the Saccharomyces cerevisae Pho84 Transceptor - The Role of Tyr179 in Functional Regulation. Journal of Biological Chemistry, 291(51), 26388-26398
Open this publication in new window or tab >>Key Residues and Phosphate Release Routes in the Saccharomyces cerevisae Pho84 Transceptor - The Role of Tyr179 in Functional Regulation
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2016 (English)In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 291, no 51, p. 26388-26398Article in journal (Refereed) Published
Abstract [en]

Pho84, a major facilitator superfamily (MFS) protein, is the main high-affinity Pi transceptor in Saccharomyces cerevisiae. Although transport mechanisms have been suggested for other MFS members, the key residues and molecular events driving transport by Pi: H+ symporters are unclear. The current Pho84 transport model is based on the inward-facing occluded crystal structure of the Pho84 homologue PiPT in the fungus Piriformospora indica. However, this model is limited by the lack of experimental data on the regulatory residues for each stage of the transport cycle. In this study, an open, inward-facing conformation of Pho84 was used to study the release of Pi. A comparison of this conformation with the model for Pi release in PiPT revealed that Tyr(179) in Pho84 (Tyr150 in PiPT) is not part of the Pi binding site. This difference may be due to a lack of detailed information on the Pi release step in PiPT. Molecular dynamics simulations of Pho84 in which a residue adjacent to Tyr(179), Asp(178), is protonated revealed a conformational change in Pho84 from an open, inward-facing state to an occluded state. Tyr(179) then became part of the binding site as was observed in the PiPT crystal structure. The importance of Tyr(179) in regulating Pi release was supported by site-directed mutagenesis and transport assays. Using trehalase activity measurements, we demonstrated that the release of Pi is a critical step for transceptor signaling. Our results add to previous studies on PiPT, creating a more complete picture of the proton-coupled Pi transport cycle of a transceptor.

Keywords
Pho84, Saccharomyces cerevisiae, Molecular dynamics, membrane protein, transport
National Category
Biochemistry and Molecular Biology Biophysics
Research subject
Chemistry, Biochemistry
Identifiers
urn:nbn:se:lnu:diva-60171 (URN)10.1074/jbc.M116.738112 (DOI)000391568200013 ()2-s2.0-85006241160 (Scopus ID)
Funder
The Crafoord Foundation, 20150874Swedish National Infrastructure for Computing (SNIC), SNIC 2014/1-404 SNIC 2015/1-444
Available from: 2017-01-24 Created: 2017-01-24 Last updated: 2018-11-02Bibliographically approved
Golker, K., Karlsson, B. C. G., Wiklander, J. G., Rosengren, A. M. & Nicholls, I. A. (2015). Hydrogen bond diversity in the pre-polymerization stage contributes to morphology and MIP-template recognition–MAA versus MMA. European Polymer Journal, 66, 558-568
Open this publication in new window or tab >>Hydrogen bond diversity in the pre-polymerization stage contributes to morphology and MIP-template recognition–MAA versus MMA
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2015 (English)In: European Polymer Journal, ISSN 0014-3057, E-ISSN 1873-1945, Vol. 66, p. 558-568Article in journal (Refereed) Published
Abstract [en]

This report demonstrates that the diversity of hydrogen bond interactions present in molecularly imprinted polymer pre-polymerization mixtures, typically associated with binding-site heterogeneity, can also contribute to morphological characteristics that may influence polymer–template recognition. Comparisons have been made between a series of bupivacaine molecularly imprinted methacrylic acid (MAA)–ethylene glycol dimethacrylate (EGDMA) copolymers and a series of analogous methyl methacrylate (MMA)–EGDMA copolymers using comprehensive molecular dynamics studies of the respective pre-polymerization mixtures, template–polymer binding studies and detailed BET surface area and BJH porosity analyses. The role of the carboxylic acid functionality of MAA, and in particular the acidic proton, in generating morphological features conducive to analyte access (slit-like rather than ink bottle-like structures) and recognition is discussed.

Place, publisher, year, edition, pages
Pergamon Press, 2015
National Category
Materials Chemistry
Research subject
Chemistry, Organic Chemistry
Identifiers
urn:nbn:se:lnu:diva-42601 (URN)10.1016/j.eurpolymj.2015.03.018 (DOI)000353854000057 ()2-s2.0-84928389138 (Scopus ID)
Available from: 2015-04-15 Created: 2015-04-15 Last updated: 2022-06-07Bibliographically approved
Olsson, G. D., Niedergall, K., Bach, M., Karlsson, B. C. G., Tovar, G. & Nicholls, I. A. (2015). Simulation of imprinted emulsion prepolymerization mixtures. Polymer journal, 47(12), 827-830
Open this publication in new window or tab >>Simulation of imprinted emulsion prepolymerization mixtures
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2015 (English)In: Polymer journal, ISSN 0032-3896, E-ISSN 1349-0540, Vol. 47, no 12, p. 827-830Article in journal (Refereed) Published
Abstract [en]

The aim of this study was to develop protocols for and evaluate the use of all-atom full system molecular dynamic (MD) simulations of emulsion systems in the development of molecularly imprinted polymers (MIPs). Here, we report on the first, to the best of our knowledge, use of all-component MD studies to simulate and evaluate MIP miniemulsion prepolymerization mixtures; in this case, the mixtures used in the synthesis of a series of MIP-nanoparticles (MIP-NPs).

National Category
Organic Chemistry
Research subject
Chemistry, Organic Chemistry
Identifiers
urn:nbn:se:lnu:diva-48813 (URN)10.1038/pj.2015.63 (DOI)000366047900008 ()2-s2.0-84949442668 (Scopus ID)
Available from: 2016-01-19 Created: 2016-01-15 Last updated: 2023-08-31Bibliographically approved
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ORCID iD: ORCID iD iconorcid.org/0000-0002-7392-0591

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