liu.seSearch for publications in DiVA
Change search
Link to record
Permanent link

Direct link
BETA
Lundström, Patrik
Publications (10 of 46) Show all publications
Niklasson, M., Otten, R., Ahlner, A., Andrésen, C., Schlagnitweit, J., Petzold, K. & Lundström, P. (2017). Comprehensive analysis of NMR data using advanced line shape fitting.. Journal of Biomolecular NMR, 69(2), 93-99
Open this publication in new window or tab >>Comprehensive analysis of NMR data using advanced line shape fitting.
Show others...
2017 (English)In: Journal of Biomolecular NMR, ISSN 0925-2738, E-ISSN 1573-5001, Vol. 69, no 2, p. 93-99Article in journal (Refereed) Published
Abstract [en]

NMR spectroscopy is uniquely suited for atomic resolution studies of biomolecules such as proteins, nucleic acids and metabolites, since detailed information on structure and dynamics are encoded in positions and line shapes of peaks in NMR spectra. Unfortunately, accurate determination of these parameters is often complicated and time consuming, in part due to the need for different software at the various analysis steps and for validating the results. Here, we present an integrated, cross-platform and open-source software that is significantly more versatile than the typical line shape fitting application. The software is a completely redesigned version of PINT ( https://pint-nmr.github.io/PINT/ ). It features a graphical user interface and includes functionality for peak picking, editing of peak lists and line shape fitting. In addition, the obtained peak intensities can be used directly to extract, for instance, relaxation rates, heteronuclear NOE values and exchange parameters. In contrast to most available software the entire process from spectral visualization to preparation of publication-ready figures is done solely using PINT and often within minutes, thereby, increasing productivity for users of all experience levels. Unique to the software are also the outstanding tools for evaluating the quality of the fitting results and extensive, but easy-to-use, customization of the fitting protocol and graphical output. In this communication, we describe the features of the new version of PINT and benchmark its performance.

Place, publisher, year, edition, pages
Springer, 2017
Keywords
Dynamics, Line shape fitting, Peak integration, Relaxation, Spectral analysis
National Category
Biochemistry and Molecular Biology Chemical Sciences
Identifiers
urn:nbn:se:liu:diva-142786 (URN)10.1007/s10858-017-0141-6 (DOI)000414206400004 ()29043470 (PubMedID)2-s2.0-85031497711 (Scopus ID)
Note

Funding agencies: Swedish Research Council [2012-5136]

Available from: 2017-11-03 Created: 2017-11-03 Last updated: 2017-12-04Bibliographically approved
Ravichandran, R., Islam, M. M., Alarcon, E. I., Samanta, A., Wang, S., Lundström, P., . . . Phopase, J. (2016). Functionalised type-I collagen as a hydrogel building block for bio-orthogonal tissue engineering applications. Journal of materials chemistry. B, 4(2), 318-326
Open this publication in new window or tab >>Functionalised type-I collagen as a hydrogel building block for bio-orthogonal tissue engineering applications
Show others...
2016 (English)In: Journal of materials chemistry. B, ISSN 2050-750X, E-ISSN 2050-7518, Vol. 4, no 2, p. 318-326Article in journal (Refereed) Published
Abstract [en]

In this study, we derivatized type I collagen without altering its triple helical conformation to allow for facile hydrogel formation via the Michael addition of thiols to methacrylates without the addition of other crosslinking agents. This method provides the flexibility needed for the fabrication of injectable hydrogels or pre-fabricated implantable scaffolds, using the same components by tuning the modulus from Pa to kPa. Enzymatic degradability of the hydrogels can also be easily fine-tuned by variation of the ratio and the type of the crosslinking component. The structural morphology reveals a lamellar structure mimicking native collagen fibrils. The versatility of this material is demonstrated by its use as a pre-fabricated substrate for culturing human corneal epithelial cells and as an injectable hydrogel for 3-D encapsulation of cardiac progenitor cells.

Place, publisher, year, edition, pages
ROYAL SOC CHEMISTRY, 2016
National Category
Physical Sciences Chemical Sciences Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-124491 (URN)10.1039/c5tb02035b (DOI)000367335200016 ()
Note

Funding Agencies|Swedish Research Council [621-2012-4286, 521-2012-5706]; NSERC; UOHI

Available from: 2016-02-02 Created: 2016-02-01 Last updated: 2017-11-30
Kukic, P., Lundström, P., Camilloni, C., Evenas, J., Akke, M. & Vendruscolo, M. (2016). Structural Insights into the Calcium-Mediated Allosteric Transition in the C-Terminal Domain of Calmodulin from Nuclear Magnetic Resonance Measurements. Biochemistry, 55(1), 19-28
Open this publication in new window or tab >>Structural Insights into the Calcium-Mediated Allosteric Transition in the C-Terminal Domain of Calmodulin from Nuclear Magnetic Resonance Measurements
Show others...
2016 (English)In: Biochemistry, ISSN 0006-2960, E-ISSN 1520-4995, Vol. 55, no 1, p. 19-28Article in journal (Refereed) Published
Abstract [en]

Calmodulin is a two-domain signaling protein that becomes activated upon binding cooperatively two pairs of calcium ions, leading to large-scale conformational changes that expose its binding site. Despite significant advances in understanding the structural biology of calmodulin functions, the mechanistic details of the conformational transition between closed and open states have remained unclear. To investigate this transition, we used a combination of molecular dynamics simulations and nuclear magnetic resonance (NMR) experiments on the Ca2+-saturated E140Q C-terminal domain variant. Using chemical shift restraints in replica-averaged metadynamics simulations, we obtained a high-resolution structural ensemble consisting of two conformational states and validated such an ensemble against three independent experimental data sets, namely, interproton nuclear Overhauser enhancements, N-15 order parameters, and chemical shift differences between the exchanging states. Through a detailed analysis of this structural ensemble and of the corresponding statistical weights, we characterized a calcium-mediated conformational transition whereby the coordination of Ca2+ by just one oxygen of the bidentate ligand E140 triggers a concerted movement of the two EF-hands that exposes the target binding site. This analysis provides atomistic insights into a possible Ca2+-mediated activation mechanism of calmodulin that cannot be achieved from static structures alone or from ensemble NMR measurements of the transition between conformations.

Place, publisher, year, edition, pages
AMER CHEMICAL SOC, 2016
National Category
Chemical Sciences
Identifiers
urn:nbn:se:liu:diva-125154 (URN)10.1021/acs.biochem.5b00961 (DOI)000368323000003 ()26618792 (PubMedID)
Note

Funding Agencies|Swedish Research Council [Dnr 2012-5136, Dnr 2010-4912]; Goran Gustafsson Foundation for Research in Natural Sciences and Medicine; Knut and Alice Wallenberg Foundation; Biotechnology and Biological Sciences Research Council [BB/H013318/1]; Federation of European Biochemical Societies Fellowship; Marie Curie Intra European Fellowship

Available from: 2016-02-15 Created: 2016-02-15 Last updated: 2017-11-30
Niklasson, M., Ahlner, A., Andrésen, C., Marsh, J. A. & Lundström, P. (2015). Fast and Accurate Resonance Assignment of Small-to-Large Proteins by Combining Automated and Manual Approaches. PloS Computational Biology, 11(1), e1004022
Open this publication in new window or tab >>Fast and Accurate Resonance Assignment of Small-to-Large Proteins by Combining Automated and Manual Approaches
Show others...
2015 (English)In: PloS Computational Biology, ISSN 1553-734X, E-ISSN 1553-7358, Vol. 11, no 1, p. e1004022-Article in journal (Refereed) Published
Abstract [en]

The process of resonance assignment is fundamental to most NMR studies of protein structure and dynamics. Unfortunately, the manual assignment of residues is tedious and time-consuming, and can represent a significant bottleneck for further characterization. Furthermore, while automated approaches have been developed, they are often limited in their accuracy, particularly for larger proteins. Here, we address this by introducing the software COMPASS, which, by combining automated resonance assignment with manual intervention, is able to achieve accuracy approaching that from manual assignments at greatly accelerated speeds. Moreover, by including the option to compensate for isotope shift effects in deuterated proteins, COMPASS is far more accurate for larger proteins than existing automated methods. COMPASS is an open-source project licensed under GNU General Public License and is available for download from http://www.liu.se/forskning/foass/tidigare-foass/patrik-lundstrom/software?l=en. Source code and binaries for Linux, Mac OS X and Microsoft Windows are available.

Place, publisher, year, edition, pages
Public Library of Science, 2015
National Category
Chemical Sciences
Identifiers
urn:nbn:se:liu:diva-115010 (URN)10.1371/journal.pcbi.1004022 (DOI)000349309400013 ()25569628 (PubMedID)
Note

Funding Agencies|Swedish Research Council [Dnr. 2012-5136]

Available from: 2015-03-09 Created: 2015-03-06 Last updated: 2017-12-04
Ahlner, A., Andresen, C., Khan, S. N., Kay, L. E. & Lundström, P. (2015). Fractional enrichment of proteins using [2-13C]-glycerol as the carbon source facilitates measurement of excited state 13Cα chemical shifts with improved sensitivity. Journal of Biomolecular NMR, 62(3), 341-351
Open this publication in new window or tab >>Fractional enrichment of proteins using [2-13C]-glycerol as the carbon source facilitates measurement of excited state 13Cα chemical shifts with improved sensitivity
Show others...
2015 (English)In: Journal of Biomolecular NMR, ISSN 0925-2738, E-ISSN 1573-5001, Vol. 62, no 3, p. 341-351Article in journal (Refereed) Published
Abstract [en]

A selective isotope labeling scheme based on the utilization of [2-13C]-glycerol as the carbon source during protein overexpression has been evaluated for the measurement of excited state 13Cα chemical shifts using Carr–Purcell–Meiboom–Gill (CPMG) relaxation dispersion (RD) experiments. As expected, the fractional incorporation of label at the Cα positions is increased two-fold relative to labeling schemes based on [2-13C]-glucose, effectively doubling the sensitivity of NMR experiments. Applications to a binding reaction involving an SH3 domain from the protein Abp1p and a peptide from the protein Ark1p establish that accurate excited state 13Cα chemical shifts can be obtained from RD experiments, with errors on the order of 0.06 ppm for exchange rates ranging from 100 to 1000 s−1, despite the small fraction of 13Cα–13Cβ spin-pairs that are present for many residue types. The labeling approach described here should thus be attractive for studies of exchanging systems using 13Cα spin probes.

Place, publisher, year, edition, pages
Springer Netherlands, 2015
Keywords
CPMG, 13Cα labeling, [2-13C]-Glycerol, Excited states
National Category
Chemical Sciences
Identifiers
urn:nbn:se:liu:diva-117073 (URN)10.1007/s10858-015-9948-1 (DOI)000357489200010 ()
Note

At the time for thesis presentation publication was in status: Manuscript

At the time for thesis presentation name of publication was: Fractional enrichment using [2-13C]-glycerol as the carbon source facilitates measurements of excited state 13Cα chemical shifts with improved sensitivity

Available from: 2015-04-15 Created: 2015-04-15 Last updated: 2017-12-04Bibliographically approved
Hennig, J., Andrésen, C., Museth, A. K., Lundström, P., Tibell, L. & Jonsson, B.-H. (2015). Local Destabilization of the Metal-Binding Region in Human Copper-Zinc Superoxide Dismutase by Remote Mutations Is a Possible Determinant for Progression of ALS. Biochemistry, 54(2), 323-333
Open this publication in new window or tab >>Local Destabilization of the Metal-Binding Region in Human Copper-Zinc Superoxide Dismutase by Remote Mutations Is a Possible Determinant for Progression of ALS
Show others...
2015 (English)In: Biochemistry, ISSN 0006-2960, E-ISSN 1520-4995, Vol. 54, no 2, p. 323-333Article in journal (Refereed) Published
Abstract [en]

More than 100 distinct mutations in the gene CuZnSOD encoding human copper-zinc superoxide dismutase (CuZnSOD) have been associated with familial amyotrophic lateral sclerosis (fALS), a fatal neuronal disease. Many studies of different mutant proteins have found effects on protein stability, catalytic activity, and metal binding, but without a common pattern. Notably, these studies were often performed under conditions far from physiological. Here, we have used experimental conditions of pH 7 and 37 degrees C and at an ionic strength of 0.2 M to mimic physiological conditions as close as possible in a sample of pure protein. Thus, by using NMR spectroscopy, we have analyzed amide hydrogen exchange of the fALS-associated I113T CuZnSOD variant in its fully metalated state, both at 25 and 37 degrees C, where (15)N relaxation data, as expected, reveals that CuZnSOD I113T exists as a dimer under these conditions. The local dynamics at 82% of all residues have been analyzed in detail. When compared to the wild-type protein, it was found that I113T CuZnSOD is particularly destabilized locally at the ion binding sites of loop 4, the zinc binding loop, which results in frequent exposure of the aggregation prone outer beta-strands I and VI of the beta-barrel, possibly enabling fibril or aggregate formation. A similar study (Museth, A. K., et al. (2009) Biochemistry, 48, 8817-8829) of amide hydrogen exchange at pH 7 and 25 degrees C on the G93A variant also revealed a selective destabilization of the zinc binding loop. Thus, a possible scenario in ALS is that elevated local dynamics at the metal binding region can result in toxic species from formation of new interactions at local beta-strands.

Place, publisher, year, edition, pages
American Chemical Society, 2015
National Category
Biological Sciences Chemical Sciences Electrical Engineering, Electronic Engineering, Information Engineering
Identifiers
urn:nbn:se:liu:diva-114994 (URN)10.1021/bi500606j (DOI)000348333300022 ()25496420 (PubMedID)
Note

Funding Agencies|Swedish Research Council [Dnr 2006-4253, Dnr 621-2012-5136]

Available from: 2015-03-09 Created: 2015-03-06 Last updated: 2017-12-04
Helander, S., Montecchio, M., Pilstål, R., Su, Y., Kuruvilla, J., Johansson, M., . . . Sunnerhagen, M. (2015). Pre-Anchoring of Pin1 to Unphosphorylated c-Myc in a Fuzzy Complex Regulates c-Myc Activity. Structure, 23(12), 2267-2279
Open this publication in new window or tab >>Pre-Anchoring of Pin1 to Unphosphorylated c-Myc in a Fuzzy Complex Regulates c-Myc Activity
Show others...
2015 (English)In: Structure, ISSN 0969-2126, E-ISSN 1878-4186, Vol. 23, no 12, p. 2267-2279Article in journal (Refereed) Published
Abstract [en]

Hierarchic phosphorylation and concomitant Pin1-mediated proline isomerization of the oncoprotein c-Myc controls its cellular stability and activity. However, the molecular basis for Pin1 recognition and catalysis of c-Myc and other multisite, disordered substrates in cell regulation and disease is unclear. By nuclear magnetic resonance, surface plasmon resonance, and molecular modeling, we show that Pin1 subdomains jointly pre-anchor unphosphorylated c-Myc1–88 in the Pin1 interdomain cleft in a disordered, or “fuzzy”, complex at the herein named Myc Box 0 (MB0) conserved region N-terminal to the highly conserved Myc Box I (MBI). Ser62 phosphorylation in MBI intensifies previously transient MBI-Pin1 interactions in c-Myc1–88 binding, and increasingly engages Pin1PPIase and its catalytic region with maintained MB0 interactions. In cellular assays, MB0 mutated c-Myc shows decreased Pin1 interaction, increased protein half-life, but lowered rates of Myc-driven transcription and cell proliferation. We propose that dynamic Pin1 recognition of MB0 contributes to the regulation of c-Myc activity in cells

Place, publisher, year, edition, pages
Cell Press, 2015
National Category
Natural Sciences
Identifiers
urn:nbn:se:liu:diva-106184 (URN)10.1016/j.str.2015.10.010 (DOI)
Note

The previous status of this article was Manuscript and the original title was Pre-anchoring of Pin1 to unphosphorylated c-Myc in a dynamic complex affects c-Myc stability andactivity.

Funding Agencies|Knut and Alice Wallenberg Foundation; Swedish Cancer Foundation; Swedish Child Cancer Foundation; Carl Trygger foundation; LiU Cancer Research Network; Swedish Research Council; NCI [R01s CA129040, CA100855]

Available from: 2014-04-28 Created: 2014-04-28 Last updated: 2018-05-06Bibliographically approved
Karlsson, E., Magic, I., Bostner, J., Dyrager, C., Lysholm, F., Hallbeck, A.-L., . . . Lundström, P. (2015). Revealing Different Roles of the mTOR-Targets S6K1 and S6K2 in Breast Cancer by Expression Profiling and Structural Analysis. PLoS ONE, 10(12), e0145013
Open this publication in new window or tab >>Revealing Different Roles of the mTOR-Targets S6K1 and S6K2 in Breast Cancer by Expression Profiling and Structural Analysis
Show others...
2015 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 12, p. e0145013-Article in journal (Refereed) Published
Abstract [en]

Background

The AKT/mTORC1/S6K pathway is frequently overstimulated in breast cancer, constituting a promising therapeutic target. The benefit from mTOR inhibitors varies, likely as a consequence of tumour heterogeneity, and upregulation of several compensatory feed-back mechanisms. The mTORC1 downstream effectors S6K1, S6K2, and 4EBP1 are amplified and overexpressed in breast cancer, associated with a poor outcome and divergent endocrine treatment benefit. S6K1 and S6K2 share high sequence homology, but evidence of partly distinct biological functions is emerging. The aim of this work was to explore possible different roles and treatment target potentials of S6K1 and S6K2 in breast cancer.

Materials and methods

Whole-genome expression profiles were compared for breast tumours expressing high levels of S6K1, S6K2 or 4EBP1, using public datasets, as well as after in vitro siRNA downregulation of S6K1 and/or S6K2 in ZR751 breast cancer cells. In silico homology modelling of the S6K2 kinase domain was used to evaluate its possible structural divergences to S6K1.

Results

Genome expression profiles were highly different in S6K1 and S6K2 high tumours, whereas S6K2 and 4EBP1 profiles showed significant overlaps, both correlated to genes involved in cell cycle progression, among these the master regulator E2F1. S6K2 and 4EBP1 were inversely associated with IGF1 levels, and their prognostic value was shown to be restricted to tumours positive for IGFR and/or HER2. In vitro, S6K1 and S6K2 silencing resulted in upregulation of genes in the mTORC1 and mTORC2 complexes. Isoform-specific silencing also showed distinct patterns, e.g. S6K2 downregulation lead to upregulation of several cell cycle associated genes. Structural analyses of the S6K2 kinase domain showed unique structure patterns, deviating from those of S6K1, facilitating the development of isoform-specific inhibitors. Our data support emerging proposals of distinct biological features of S6K1 and S6K2, suggesting their importance as separate oncogenes and clinical markers, where specific targeting in different breast cancer subtypes could facilitate further individualised therapies.

Place, publisher, year, edition, pages
Public Library Science, 2015
National Category
Clinical Medicine Biological Sciences Chemical Sciences
Identifiers
urn:nbn:se:liu:diva-124494 (URN)10.1371/journal.pone.0145013 (DOI)000367092600042 ()26698305 (PubMedID)
Note

At the time for thesis presentation publication was in status: Manuscript

Funding Agencies|Swedish Research Council [2012-5136, 2007-3475]; Swedish Cancer Foundation; LiU Cancer; LiU Cancer Foundation

Available from: 2016-02-02 Created: 2016-02-01 Last updated: 2017-11-30Bibliographically approved
Niklasson, M., Andrésen, C., Helander, S., Roth, M., Zimdahl Kahlin, A., Lindqvist Appell, M., . . . Lundström, P. (2015). Robust and convenient analysis of protein thermal and chemical stability. Protein Science, 24(12), 2055-2062
Open this publication in new window or tab >>Robust and convenient analysis of protein thermal and chemical stability
Show others...
2015 (English)In: Protein Science, ISSN 0961-8368, E-ISSN 1469-896X, Vol. 24, no 12, p. 2055-2062Article in journal (Refereed) Published
Abstract [en]

We present the software CDpal that is used to analyze thermal and chemical denaturation data to obtain information on protein stability. The software uses standard assumptions and equations applied to two-state and various types of three-state denaturation models in order to determine thermodynamic parameters. It can analyze denaturation monitored by both circular dichroism and fluorescence spectroscopy and is extremely flexible in terms of input format. Furthermore, it is intuitive and easy to use because of the graphical user interface and extensive documentation. As illustrated by the examples herein, CDpal should be a valuable tool for analysis of protein stability.

Place, publisher, year, edition, pages
WILEY-BLACKWELL, 2015
Keywords
protein stability; thermal denaturation; chemical denaturation; circular dichroism; fluorescence; curve fitting; protein stability software; protein denaturation software
National Category
Chemical Sciences Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-124648 (URN)10.1002/pro.2809 (DOI)000368292000014 ()26402034 (PubMedID)
Note

Funding Agencies|Swedish Research Council [2012-5136]; LiU Cancer

Available from: 2016-02-08 Created: 2016-02-08 Last updated: 2017-11-30
Anandapadmanaban, M., Andrésen, C., Helander, S., Ohyama, Y., Siponen, M. I., Lundström, P., . . . Sunnerhagen, M. (2013). High-resolution structure of TBP with TAF1 reveals anchoring patterns in transcriptional regulation. Nature Structural & Molecular Biology, 20(8), 1008-+
Open this publication in new window or tab >>High-resolution structure of TBP with TAF1 reveals anchoring patterns in transcriptional regulation
Show others...
2013 (English)In: Nature Structural & Molecular Biology, ISSN 1545-9993, E-ISSN 1545-9985, Vol. 20, no 8, p. 1008-+Article in journal (Refereed) Published
Abstract [en]

The general transcription factor TFIID provides a regulatory platform for transcription initiation. Here we present the crystal structure (1.97 angstrom) and NMR analysis of yeast TAF1 N-terminal domains TAND1 and TAND2 bound to yeast TBP, together with mutational data. We find that yeast TAF1-TAND1, which in itself acts as a transcriptional activator, binds TBPs concave DNA-binding surface by presenting similar anchor residues to TBP as does Mot1 but from a distinct structural scaffold. Furthermore, we show how TAF1-TAND2 uses an aromatic and acidic anchoring pattern to bind a conserved TBP surface groove traversing the basic helix region, and we find highly similar TBP-binding motifs also presented by the structurally distinct TFIIA, Mot1 and Brf1 proteins. Our identification of these anchoring patterns, which can be easily disrupted or enhanced, provides insight into the competitive multiprotein TBP interplay critical to transcriptional regulation.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP, 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA, 2013
National Category
Engineering and Technology
Identifiers
urn:nbn:se:liu:diva-96977 (URN)10.1038/nsmb.2611 (DOI)000322715300016 ()
Note

Funding Agencies|Swedish Research Council|621-2011-6028621-2012-5250621-2012-5136|VINNOVA|P32045-1|Swedish Cancer Foundation|11 0681|Swedish Child Cancer Foundation|PROJ09/092|Forum Scientium Award||Canadian Institutes for Health Research|MT-13611|Japan Society for the Promotion of Science|23370077|Knut and Alice Wallenberg foundation||Canada Research Chair||

Available from: 2013-09-05 Created: 2013-09-02 Last updated: 2017-12-06
Organisations

Search in DiVA

Show all publications