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Lundqvist, Martin
Alternative names
Publications (10 of 15) Show all publications
Nygren, P., Lundqvist, M., Liedberg, B., Broo, K., Jonsson, B.-H. & Ederth, T. (2011). Secondary structure in de novo designed peptides induced by electrostatic interaction with particles and membranes.. In: : . Paper presented at Workshop BILL2011 - Bilayers at the Institut Laue Langevin (ILL), Grenoble, France, January 12th - 14th 2011.
Open this publication in new window or tab >>Secondary structure in de novo designed peptides induced by electrostatic interaction with particles and membranes.
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2011 (English)Conference paper, Poster (with or without abstract) (Other academic)
National Category
Physical Sciences
Identifiers
urn:nbn:se:liu:diva-122696 (URN)
Conference
Workshop BILL2011 - Bilayers at the Institut Laue Langevin (ILL), Grenoble, France, January 12th - 14th 2011
Available from: 2015-11-16 Created: 2015-11-16 Last updated: 2017-01-11Bibliographically approved
Nygren, P., Lundqvist, M., Liedberg, B., Jonsson, B.-H. & Ederth, T. (2010). Secondary Structure in de Novo Designed Peptides Induced by Electrostatic Interaction with a Lipid Bilayer Membrane. LANGMUIR, 26(9), 6437-6448
Open this publication in new window or tab >>Secondary Structure in de Novo Designed Peptides Induced by Electrostatic Interaction with a Lipid Bilayer Membrane
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2010 (English)In: LANGMUIR, ISSN 0743-7463, Vol. 26, no 9, p. 6437-6448Article in journal (Refereed) Published
Abstract [en]

We show that it is possible to induce a defined secondary structure in de nova designed peptides upon electrostatic attachment to negatively charged lipid bilayer vesicles without partitioning of the peptides into the membrane, and that the secondary structure can be varied via small changes in the primary amino acid sequence of the peptides. The peptides have a random-coil conformation in solution, and results from far-UV circular dichroism spectroscopy demonstrate that the structure induced by the interaction with silica nanoparticles is solely alpha-helical and also strongly pH-dependent. The present study shows that negatively charged vesicles, to which the peptides are electrostatically adsorbed via cationic amino acid residues, induce either alpha-helices or beta-sheets and that the conformation is dependent on both lipid composition and variations in peptide primary structure. The pH-dependence of the vesicle-induced peptide secondary structure is weak, which correlates well with small differences in the vesicles electrophoretic mobility, and thus the surface charge, as the pH is varied.

Place, publisher, year, edition, pages
ACS American Chemical Society, 2010
National Category
Engineering and Technology
Identifiers
urn:nbn:se:liu:diva-56297 (URN)10.1021/la100027n (DOI)000276969700056 ()
Note

The previous status of this article was Manuscript.

Available from: 2010-05-07 Created: 2010-05-07 Last updated: 2017-01-11
Museth, A. K., Brorsson, A.-C., Lundqvist, M., Tibell, L. & Jonsson, B.-H. (2009). The ALS-Associated Mutation G93A in Human Copper-Zinc Superoxide Dismutase Selectively Destabilizes the Remote Metal Binding Region. BIOCHEMISTRY, 48(37), 8817-8829
Open this publication in new window or tab >>The ALS-Associated Mutation G93A in Human Copper-Zinc Superoxide Dismutase Selectively Destabilizes the Remote Metal Binding Region
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2009 (English)In: BIOCHEMISTRY, ISSN 0006-2960, Vol. 48, no 37, p. 8817-8829Article in journal (Refereed) Published
Abstract [en]

More than 100 distinct mutations in the gene (SOD 1) for human copper-zinc superoxide dismutase (CuZnSOD) have been associated with familial amyotrophic lateral sclerosis (fALS). Studies of these mutant proteins, which often have been performed under far from physiological conditions, have indicated effects oil protein stabilities, catalytic activity, kind metal binding affinities but with no common pattern. Also, with the knowledge that ALS is a late onset disease it is apparent that protein interactions which contribute to the disorder might, in the natural cellular milieu, depend on a delicate balance between intrinsic protein properties. In this study, we have used experimental conditions as near as possible to the in vivo conditions to reduce artifacts emanating from the experimental setup. Using H-1-N-15 HSQC NMR spectroscopy, we have analyzed hydrogen exchange at the amide groups of wild-type (wt) CuZnSOD and the fALS-associated G93A SOD variant in their fully metalated states. From analyses of the exchange pattern, we have characterized the local dynamics at 64% of all positions in detail in both the wt and G93A protein. The results show that the G93A mutation had no effect on the dynamics at a majority of the investigated positions. However, the mutation results in local destabilization at the site of the Mutation and also in stabilization at a few positions that were apparently scattered over the entire protein surface. Most remarkably, the mutation selectively destabilized the remote metal binding region. The results indicate that the metal binding region may affect the intermolecular protein-protein interactions which cause formation of protein aggregates.

National Category
Natural Sciences
Identifiers
urn:nbn:se:liu:diva-20909 (URN)10.1021/bi900703v (DOI)
Available from: 2009-09-26 Created: 2009-09-25 Last updated: 2016-05-04
Jonsson, B.-H., Broo, K., Lundqvist, M. & Nygren, P. (2008). Design of Functional Peptide-Nanoparticle Complexes with Potential Applications in Targeted Drug Delivery. In: BITs 6th annual congress of 2008 International drug discovery science and technology,2008 (pp. 142-143).
Open this publication in new window or tab >>Design of Functional Peptide-Nanoparticle Complexes with Potential Applications in Targeted Drug Delivery
2008 (English)In: BITs 6th annual congress of 2008 International drug discovery science and technology,2008, 2008, p. 142-143Conference paper, Published paper (Other academic)
Keywords
Nanotechnology, biotechnology, drug delivery
National Category
Natural Sciences
Identifiers
urn:nbn:se:liu:diva-45311 (URN)81051 (Local ID)81051 (Archive number)81051 (OAI)
Available from: 2009-10-10 Created: 2009-10-10
Nygren, P., Lundqvist, M., Broo, K. & Jonsson, B.-H. (2008). Fundamental Design Principles That Guide Induction of Helix upon Formation of Stable Peptide−Nanoparticle Complexes. Nano letters (Print), 8(7), 1844-1852
Open this publication in new window or tab >>Fundamental Design Principles That Guide Induction of Helix upon Formation of Stable Peptide−Nanoparticle Complexes
2008 (English)In: Nano letters (Print), ISSN 1530-6984, E-ISSN 1530-6992, Vol. 8, no 7, p. 1844-1852Article in journal (Refereed) Published
Abstract [en]

We have shown that it is possible to design a peptide that has a very low helical content when free in solution but that adopts a well-defined helix when interacting with silica nanoparticles. From a systematic variation of the amino acid composition and distribution in designed peptides, it has been shown that the ability to form helical structure upon binding to the silica surface is dominated by two factors. First, the helical content is strongly correlated with the net positive charge on the side of the helix that interacts with the silica, and arginine residues are strongly favored over lysine residues in these positions. The second important factor is to have a high net negative charge on the side of the helix that faces the solution. Apparently, both attractive and repulsive electrostatic forces dominate the induction and stabilization of a bound helix. It is also evident that using amino acids that have high propensity to form helix in solution are also advantageous for the formation of helix on surfaces.

National Category
Other Basic Medicine
Identifiers
urn:nbn:se:liu:diva-15015 (URN)10.1021/nl080386s (DOI)
Available from: 2008-10-09 Created: 2008-10-09 Last updated: 2018-01-12Bibliographically approved
Brorsson, A.-C., Lundqvist, M., Sethson, I. & Jonsson, B.-H. (2006). GuHCl and NaCl-dependent hydrogen exchange in MerP reveals a well-defined core with an unusual exchange pattern. Journal of Molecular Biology, 357(5), 1634-1646
Open this publication in new window or tab >>GuHCl and NaCl-dependent hydrogen exchange in MerP reveals a well-defined core with an unusual exchange pattern
2006 (English)In: Journal of Molecular Biology, ISSN 0022-2836, E-ISSN 1089-8638, Vol. 357, no 5, p. 1634-1646Article in journal (Refereed) Published
Abstract [en]

We have analysed hydrogen exchange at amide groups to characterise the energy landscape of the 72 amino acid residue protein MerP. From the guanidine hydrochloride (GuHCl) dependence of exchange in the pre-transitional region we have determined free energy values of exchange (ΔGHX) and corresponding m-values for individual amide protons. Detailed analysis of the exchange patterns indicates that for one set of amide protons there is a weak dependence on denaturant, indicating that the exchange is dominated by local fluctuations. For another set of amide protons a linear, but much stronger, denaturant dependence is observed. Notably, the plots of free energy of exchange versus [GuHCl] for 16 amide protons show pronounced upward curvature, and a close inspection of the structure shows that these residues form a well-defined core in the protein. The hydrogen exchange that was measured at various concentrations of NaCl shows an apparent selective stabilisation of this core. Detailed analysis of this exchange pattern indicates that it may originate from selective destabilisation of the unfolded state by guanidinium ions and/or selective stabilisation of the core in the native state by chloride ions. © 2006 Elsevier Ltd. All rights reserved.

National Category
Natural Sciences
Identifiers
urn:nbn:se:liu:diva-36287 (URN)10.1016/j.jmb.2006.01.090 (DOI)30876 (Local ID)30876 (Archive number)30876 (OAI)
Available from: 2009-10-10 Created: 2009-10-10 Last updated: 2017-12-13
Lundqvist, M., Nygren, P., Jonsson, B.-H. & Broo, K. (2006). Induction of structure and function in a designed peptide upon adsorption on a silica nanoparticle. Angewandte Chemie International Edition, 45(48), 8169-8173
Open this publication in new window or tab >>Induction of structure and function in a designed peptide upon adsorption on a silica nanoparticle
2006 (English)In: Angewandte Chemie International Edition, ISSN 1433-7851, E-ISSN 1521-3773, Vol. 45, no 48, p. 8169-8173Article in journal (Refereed) Published
Abstract [en]

No abstrack available.

Keywords
Amino acids, catalysis, helical structures, nanoparticles, peptides
National Category
Chemical Sciences
Identifiers
urn:nbn:se:liu:diva-14548 (URN)10.1002/anie.200600965 (DOI)
Available from: 2008-02-25 Created: 2008-02-25 Last updated: 2017-12-13Bibliographically approved
Lundqvist, M. (2005). Conformation of polypeptides at nanoparticles interfaces: protein structural changes and induced folding of peptides. (Doctoral dissertation). Linköping: Linköpings universitet
Open this publication in new window or tab >>Conformation of polypeptides at nanoparticles interfaces: protein structural changes and induced folding of peptides
2005 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

This thesis can be divided into two parts. The first deals with characterization of structural and dynamic consequences for proteins of interactions with a solid surface in the form of silica nanoparticles. The studies were conducted on isoenzymes and mutant variants of Human Carbonic Anhydrase that have virtually identical topology but differ considerably with respect to stability. The nanoparticles were chosen as the solid phase because their small sizes allow the use of spectroscopic techniques that are usually employed to study molecular interactions in solution.

CD measurements of the interactions between HCAI and nanoparticles with different diameters show that the perturbation of the secondary structure is dependent on the curvature of the nanoparticle. A relatively flat surface causes greater perturbation because it allows a larger interaction area with the. protein than a curved surface. Use of the TROSY pulse sequence allowed NMR spectra of a large stable complex of HCAII and solid nanoparticles to be recorded. The NMR study confirmed earlier conclusions based on CD measurements that HCAII undergoes major structural rearrangements upon binding to the nanoparticles and that the protein continues to rearrange for at least two weeks after binding. Sedimentation equilibrium AUC and gel permeation chromatography experiments established that HCAI is in a true equilibrium between forms that are free and forms that are bound to the nanoparticles for at least seven days. NMR studies of HCAI-nanoparticle systems showed that residues in the central ß-strands of HCAI do not regain their native conformation during the time they are dissociated from the nanoparticles i.e. information about the bound state were gleaned from studies of free molecules. Further NMR studies showed that the perturbations persist for long time even after removal of the nanoparticles from the solution. Surprisingly, the conformational heterogeneity did not disturb the delicate positioning of the active site residues that is required for full catalytic activity. A novel approach was used to characterize the initial binding of HCAII to the nanoparticles and subsequent structural alterations of the protein. MALDI-TOP mass spectrometry was used to analyse the fragment patterns after proteolytic cleavage in the presence of nanoparticles and the results were compared with corresponding fragment pattern for a native sample. The initial binding site of HCAII was shown to include parts of the N- and C-termini and the major subsequent structural rearrangements were also characterized.

The second part of this thesis concerns an approach to use surface interaction to regulate the structure and function of designed peptides. Using de novo design, a peptide was constructed that would be unstructured in solution, but would be "forced" to adopt a well-defmed helical structure following adsorption to silica nanoparticles. Moreover, the design also included precisely placed amino acids that were intended to form a functional catalytic site upon induction of the helix on the surface of the nanoparticles. Characterization of the structure and function of the designed peptide using CD and activity measurements show that the nanoparticles can be used, as intended, to induce structure in the peptide and switch on the catalytic function.

Place, publisher, year, edition, pages
Linköping: Linköpings universitet, 2005. p. 49
Series
Linköping Studies in Science and Technology. Dissertations, ISSN 0345-7524 ; 926
National Category
Natural Sciences
Identifiers
urn:nbn:se:liu:diva-24573 (URN)6746 (Local ID)91-852-9749-6 (ISBN)6746 (Archive number)6746 (OAI)
Public defence
2005-03-11, Planck, Fysikhuset, Linköpings Universitet, Linköping, 09:15 (Swedish)
Opponent
Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2012-11-16
Lundqvist, M., Sethson, I. & Jonsson, B.-H. (2005). High-Resolution 2D 1H−15N NMR Characterization of Persistent Structural Alterations of Proteins Induced by Interactions with Silica Nanoparticles. Langmuir, 21(13), 5974-5979
Open this publication in new window or tab >>High-Resolution 2D 1H−15N NMR Characterization of Persistent Structural Alterations of Proteins Induced by Interactions with Silica Nanoparticles
2005 (English)In: Langmuir, ISSN 0743-7463, E-ISSN 1520-5827, Vol. 21, no 13, p. 5974-5979Article in journal (Refereed) Published
Abstract [en]

The binding of protein to solid surfaces often induces changes in the structure, and to investigate these matters we have selected two different protein−nanoparticle systems. The first system concerns the enzyme human carbonic anhydrase II which binds essentially irreversibly to the nanoparticles, and the second system concerns human carbonic anhydrase I which alternate between the adsorbed and free state upon interaction with nanoparticles. Application of the TROSY pulse sequence has allowed high-resolution NMR analysis for both of the protein−nanoparticle systems. For HCAII it was possible to observe spectra of protein when bound to the nanoparticles. The results indicated that HCAII undergoes large rearrangements, forming an ensemble of molten globule-like structures on the surface. The spectra from the HCAI−nanoparticle system are dominated by HCAI molecules in solution. A comparative analysis of variations in intensity from 97 amide resonances in a 1H−15N TROSY spectrum revealed the effects from interaction with nanoparticle on the protein structure at amino acid resolution.

National Category
Natural Sciences
Identifiers
urn:nbn:se:liu:diva-30402 (URN)10.1021/la050569j (DOI)15958 (Local ID)15958 (Archive number)15958 (OAI)
Available from: 2009-10-09 Created: 2009-10-09 Last updated: 2017-12-13
Lundqvist, M., Andrésen, C., Christensson, S., Johansson, S., Karlsson, M., Broo, K. & Jonsson, B.-H. (2005). Proteolytic cleavage reveals interaction patterns between silica nanoparticles and two variants of human carbonic anhydrase. Langmuir, 21(25), 11903-11906
Open this publication in new window or tab >>Proteolytic cleavage reveals interaction patterns between silica nanoparticles and two variants of human carbonic anhydrase
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2005 (English)In: Langmuir, ISSN 0743-7463, E-ISSN 1520-5827, Vol. 21, no 25, p. 11903-11906Article in journal (Refereed) Published
Abstract [en]

To characterize the sites on the protein surface that are involved in the adsorption to silica nanoparticles and the subsequent rearrangements of the protein/nanoparticle interaction, a novel approach has been used. After incubation of protein with silica nanoparticles for 2 or 16 h, the protein was cleaved with trypsin and the peptide fragments were analyzed with mass spectrometry. The nanoparticle surface area was in 16-fold excess over available protein surface to minimize the probability that the initial binding would be affected by other protein molecules. When the fragment patterns obtained in the presence and absence of silica nanoparticles were compared, we were able to characterize the protein fragments that interact with the surface. This approach has allowed us to identify the initial binding sites on the protein structure and the rearrangement of the binding sites that occur upon prolonged incubation with the surface.

National Category
Engineering and Technology
Identifiers
urn:nbn:se:liu:diva-50344 (URN)10.1021/la050477u (DOI)
Available from: 2009-10-11 Created: 2009-10-11 Last updated: 2017-12-12
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