Change search
Refine search result
1 - 13 of 13
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the Create feeds function.
  • 1.
    Björkholm, Patrik
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Protein Interactions from the Molecular to the Domain Level2014Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The basic unit of life is the cell, from single-cell bacteria to the largest creatures on the planet. All cells have DNA, which contains the blueprint for proteins. This information is transported in the form of messenger RNA from the genome to ribosomes where proteins are produced. Proteins are the main functional constituents of the cell, they usually have one or several functions and are the main actors in almost all essential biological processes. Proteins are what make the cell alive. Proteins are found as solitary units or as part of large complexes. Proteins can be found in all parts of the cell, the most common place being the cytoplasm, a central space in all cells. They are also commonly found integrated into or attached to various membranes.

    Membranes define the cell architecture. Proteins integrated into the membrane have a wide number of responsibilities: they are the gatekeepers of the cell, they secrete cellular waste products, and many of them are receptors and enzymes.

    The main focus of this thesis is the study of protein interactions, from the molecular level up to the protein domain level.

    In paper I use reoccurring local protein structures to try and predict what sections of a protein interacts with another part using only sequence information. In papers II and III we use a randomization approach on a membrane protein motif that we know interacts with a sphingomyelin lipid to find other candidate proteins that interact with sphingolipids. These are then experimentally verified as sphingolipid-binding. In the last paper, paper IV, we look at how protein domain interaction networks overlap and can be evaluated.

    Download full text (pdf)
    fulltext
  • 2.
    Björkholm, Patrik
    et al.
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Daniluk, Pawel
    Kryshtafovych, Andriy
    Fidelis, Krzysztof
    Andersson, Robin
    Hvidsten, Torgeir R.
    Using multi-data hidden Markov models trained on local neighborhoods of protein structure to predict residue-residue contacts2009In: Bioinformatics, ISSN 1367-4803, E-ISSN 1367-4811, Vol. 25, no 10, p. 1264-1270Article in journal (Refereed)
    Abstract [en]

    Motivation: Correct prediction of residue-residue contacts in proteins that lack good templates with known structure would take ab initio protein structure prediction a large step forward. The lack of correct contacts, and in particular long-range contacts, is considered the main reason why these methods often fail. Results: We propose a novel hidden Markov model (HMM)based method for predicting residue-residue contacts from protein sequences using as training data homologous sequences, predicted secondary structure and a library of local neighborhoods (local descriptors of protein structure). The library consists of recurring structural entities incorporating short-, medium- and long-range interactions and is general enough to reassemble the cores of nearly all proteins in the PDB. The method is tested on an external test set of 606 domains with no significant sequence similarity to the training set as well as 151 domains with SCOP folds not present in the training set. Considering the top 0.2 . L predictions (L = sequence length), our HMMs obtained an accuracy of 22.8% for long-range interactions in new fold targets, and an average accuracy of 28.6% for long-, medium- and short- range contacts. This is a significant performance increase over currently available methods when comparing against results published in the literature.

  • 3.
    Björkholm, Patrik
    et al.
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Ernst, Andreas
    Hacke, Moritz
    Wieland, Felix
    Brügger, Britta
    von Heijne, Gunnar
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Identification of novel sphingolipid-binding motifs in mammalian membrane proteinsManuscript (preprint) (Other academic)
    Abstract [en]

    Specific interactions between transmembrane proteins and sphingolipids is a poorly understood phenomenon, and only a couple of instances have been identified. The best characterized example is the sphingolipid-binding motif VXXTLXXIY found in the transmembrane helix of the vesicular transport protein p24. Here, we have used a simple motif- probability algorithm (MOPRO) to identify proteins that contain putative sphingolipid-binding motifs in a dataset comprising full proteomes from mammalian organisms. Four selected candidate proteins all tested positive for sphingolipid binding in a photoaffinity assay. The putative sphingolipid-binding motifs are noticeably enriched in the 7TM family of G-protein coupled receptors, predominantly in transmembrane helix 6. 

  • 4.
    Björkholm, Patrik
    et al.
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab).
    Ernst, Andreas M.
    Hacke, Moritz
    Wieland, Felix
    Bruegger, Britta
    von Heijne, Gunnar
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab).
    Identification of novel sphingolipid-binding motifs in mammalian membrane proteins2014In: Biochimica et Biophysica Acta - Biomembranes, ISSN 0005-2736, E-ISSN 1879-2642, Vol. 1838, no 8, p. 2066-2070Article in journal (Refereed)
    Abstract [en]

    Specific interactions between transmembrane proteins and sphingolipids is a poorly understood phenomenon, and only a couple of instances have been identified. The best characterized example is the sphingolipid-binding motif VXXTLXXIY found in the transmembrane helix of the vesicular transport protein p24. Here, we have used a simple motif-probability algorithm (MOPRO) to identify proteins that contain putative sphingolipid-binding motifs in a dataset comprising proteomes from mammalian organisms. From these motif-containing candidate proteins, four with different numbers of transmembrane helices were selected for experimental study: i) major histocompatibility complex II Q alpha chain subtype (DQA1), ii) GPI-attachment protein 1 (GAA1), iii) tetraspanin-7 TSN7, and iv), metabotropic glutamate receptor 2 (GRM2). These candidates were subjected to photo-affinity labeling using radiolabeled sphingolipids, confirming all four candidate proteins as sphingolipid-binding proteins. The sphingolipid-binding motifs are enriched in the 7TM family of G-protein coupled receptors, predominantly in transmembrane helix 6. The ability of the motif-containing candidate proteins to bind sphingolipids with high specificity opens new perspectives on their respective regulation and function.

  • 5.
    Björkholm, Patrik
    et al.
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Sonnhammer, Erik L L
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Comparative analysis and unification of domain-domain interaction networks2009In: Bioinformatics, ISSN 1367-4803, E-ISSN 1367-4811, Vol. 25, no 22, p. 3020-5Article in journal (Refereed)
    Abstract [en]

    MOTIVATION: Certain protein domains are known to preferentially interact with other domains. Several approaches have been proposed to predict domain-domain interactions, and over nine datasets are available. Our aim is to analyse the coverage and quality of the existing resources, as well as the extent of their overlap. With this knowledge, we have the opportunity to merge individual domain interaction networks to construct a comprehensive and reliable database. RESULTS: In this article we introduce a new approach towards comparing domain-domain interaction networks. This approach is used to compare nine predicted domain and protein interaction networks. The networks were used to generate a database of unified domain interactions, UniDomInt. Each interaction in the dataset is scored according to the benchmarked reliability of the sources. The performance of UniDomInt is an improvement compared to the underlying source networks and to another composite resource, Domine. AVAILABILITY: http://sonnhammer.sbc.su.se/download/UniDomInt/

  • 6.
    Botelho, Salome
    et al.
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Österberg, Marie
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Reichert, Andreas
    Yamano, Koju
    Björkholm, Patrik
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Endo, Toshiya
    von Heijne, Gunnar
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Kim, Hyun
    Insertion of model helices into the mitochondrial inner membrane: the rules of the gameManuscript (preprint) (Other academic)
  • 7.
    Botelho, Salomé Calado
    et al.
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Österberg, Marie
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Reichert, Andreas S.
    Yamano, Koji
    Björkholm, Patrik
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Endo, Toshiya
    von Heijne, Gunnar
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Kim, Hyun
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    TIM23-mediated insertion of transmembrane alpha-helices into the mitochondrial inner membrane2011In: EMBO Journal, ISSN 0261-4189, E-ISSN 1460-2075, Vol. 30, no 6, p. 1003-1011Article in journal (Refereed)
    Abstract [en]

    While overall hydrophobicity is generally recognized as the main characteristic of transmembrane (TM) alpha-helices, the only membrane system for which there are detailed quantitative data on how different amino acids contribute to the overall efficiency of membrane insertion is the endoplasmic reticulum (ER) of eukaryotic cells. Here, we provide comparable data for TIM23-mediated membrane protein insertion into the inner mitochondrial membrane of yeast cells. We find that hydrophobicity and the location of polar and aromatic residues are strong determinants of membrane insertion. These results parallel what has been found previously for the ER. However, we see striking differences between the effects elicited by charged residues flanking the TM segments when comparing the mitochondrial inner membrane and the ER, pointing to an unanticipated difference between the two insertion systems.

  • 8. Contreras, F.-Xabier
    et al.
    Ernst, Andreas M.
    Haberkant, Per
    Björkholm, Patrik
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Lindahl, Erik
    Gönen, Basak
    Tischer, Christian
    Elofsson, Arne
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    von Heijne, Gunnar
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Thiele, Christoph
    Pepperkok, Rainer
    Wieland, Felix
    Brügger, Britta
    Molecular recognition of a single sphingolipid species by a protein’s transmembrane domain2012In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 481, no 7382, p. 525-529Article in journal (Refereed)
    Abstract [en]

    Functioning and processing of membrane proteins critically depend on the way their transmembrane segments are embedded in the membrane. Sphingolipids are structural components of membranes and can also act as intracellular second messengers. Not much is known of sphingolipids binding to transmembrane domains (TMDs) of proteins within the hydrophobic bilayer, and how this could affect protein function. Here we show a direct and highly specific interaction of exclusively one sphingomyelin species, SM 18, with the TMD of the COPI machinery protein p24 (ref. 2). Strikingly, the interaction depends on both the headgroup and the backbone of the sphingolipid, and on a signature sequence (VXXTLXXIY) within the TMD. Molecular dynamics simulations show a close interaction of SM 18 with the TMD. We suggest a role of SM 18 in regulating the equilibrium between an inactive monomeric and an active oligomeric state of the p24 protein, which in turn regulates COPI-dependent transport. Bioinformatic analyses predict that the signature sequence represents a conserved sphingolipid-binding cavity in a variety of mammalian membrane proteins. Thus, in addition to a function as second messengers, sphingolipids can act as cofactors to regulate the function of transmembrane proteins. Our discovery of an unprecedented specificity of interaction of a TMD with an individual sphingolipid species adds to our understanding of why biological membranes are assembled from such a large variety of different lipids.

    Download full text (pdf)
    fulltext
  • 9.
    Galian-Barrueco, Carmen
    et al.
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Björkholm, Patrik
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Bulleid, Neil
    von Heijne, Gunnar
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Efficient Glycosylphosphatidylinositol (GPI) Modification of Membrane Proteins Requires a C-terminal Anchoring Signal of Marginal Hydrophobicity2012In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 287, no 20, p. 16399-16409Article in journal (Refereed)
    Abstract [en]

    Many plasma membrane proteins are anchored to the membrane via a C-terminal glycosylphosphatidylinositol (GPI) moiety. The GPI anchor is attached to the protein in the endoplasmic reticulum by transamidation, a reaction in which a C-terminal GPI-attachment signal is cleaved off concomitantly with addition of the GPI moiety. GPI-attachment signals are poorly conserved on the sequence level but are all composed of a polar segment that includes the GPI-attachment site followed by a hydrophobic segment located at the very C terminus of the protein. Here, we show that efficient GPI modification requires that the hydrophobicity of the C-terminal segment is marginal: less hydrophobic than type II transmembrane anchors and more hydrophobic than the most hydrophobic segments found in secreted proteins. We further show that the GPI-attachment signal can be modified by the transamidase irrespective of whether it is first released into the lumen of the endoplasmic reticulum or is retained in the endoplasmic reticulum membrane.

  • 10.
    Larsson, Per
    et al.
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Björkholm, Patrik
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Wallner, Björn
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Lindahl, Erik
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Elofsson, Arne
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Comparison of the efficiency of different protein structure refinement techniques2010Manuscript (preprint) (Other academic)
  • 11.
    Maddalo, Gianluca
    et al.
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Stenberg-Bruzell, Filippa
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Götzke, Hansjörg
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Toddo, Stephen
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Patrik, Björkholm
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Eriksson, Hanna
    Chovanec, Peter
    Genevaux, Pierre
    Lehtiö, Janne
    Ilag, Leopold L.
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Daley, Daniel O.
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Systematic Analysis of Native Membrane Protein Complexes in Escherichia coli2011In: Journal of Proteome Research, ISSN 1535-3893, E-ISSN 1535-3907, Vol. 10, no 4, p. 1848-1859Article in journal (Refereed)
    Abstract [en]

    The cell envelope of Escherichia coli is an essential structure that modulates exchanges between the cell and the extra-cellular milieu. Previous proteomic analyses have suggested that it contains a significant number of proteins with no annotated function. To gain insight into these proteins and the general organization of the cell envelope proteome, we have carried out a systematic analysis of native membrane protein complexes. We have identified 30 membrane protein complexes (6 of which are novel) and present reference maps that can be used for cell envelope profiling. In one instance, we identified a protein with no annotated function (YfgM) in a complex with a well-characterized periplasmic chaperone (PpiD). Using the guilt by association principle, we suggest that YfgM is also part of the periplasmic chaperone network. The approach we present circumvents the need for engineering of tags and protein overexpression. It is applicable for the analysis of membrane protein complexes in any organism and will be particularly useful for less-characterized organisms where conventional strategies that require protein engineering (i.e., 2-hybrid based approaches and TAP-tagging) are not feasible.

  • 12. Morana, Ornella
    et al.
    Nieto-Garai, Jon Ander
    Björkholm, Patrik
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    de la Serna, Jorge Bernardino
    Terrones, Oihana
    Arboleya, Aroa
    Ciceri, Dalila
    Rojo-Bartolomé, Iratxe
    Blouin, Cédric M.
    Lamaze, Christophe
    Lorizate, Maier
    Contreras, Francesc-Xabier
    Identification of a New Cholesterol-Binding Site within the IFN-γ Receptor that is Required for Signal Transduction2022In: Advanced Science, E-ISSN 2198-3844, Vol. 9, no 11, article id 2105170Article in journal (Refereed)
    Abstract [en]

    The cytokine interferon-gamma (IFN-γ) is a master regulator of innate and adaptive immunity involved in a broad array of human diseases that range from atherosclerosis to cancer. IFN-γ exerts it signaling action by binding to a specific cell surface receptor, the IFN-γ receptor (IFN-γR), whose activation critically depends on its partition into lipid nanodomains. However, little is known about the impact of specific lipids on IFN-γR signal transduction activity. Here, a new conserved cholesterol (chol) binding motif localized within its single transmembrane domain is identified. Through direct binding, chol drives the partition of IFN-γR2 chains into plasma membrane lipid nanodomains, orchestrating IFN-γR oligomerization and transmembrane signaling. Bioinformatics studies show that the signature sequence stands for a conserved chol-binding motif presented in many mammalian membrane proteins. The discovery of chol as the molecular switch governing IFN-γR transmembrane signaling represents a significant advance for understanding the mechanism of lipid selectivity by membrane proteins, but also for figuring out the role of lipids in modulating cell surface receptor function. Finally, this study suggests that inhibition of the chol-IFNγR2 interaction may represent a potential therapeutic strategy for various IFN-γ-dependent diseases. 

  • 13.
    Reithinger, Johannes H
    et al.
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Yim, Chewon
    Seoul National University.
    Park, Kwangjin
    Seoul National University.
    Björkholm, Patrik
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    von Heijne, Gunnar
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Kim, Hyun
    Seoul National University, Seoul, South Korea.
    A short C-terminal tail prevents mis-targeting of hydrophobic mitochondrial membrane proteins to the ER2013In: FEBS Letters, ISSN 0014-5793, E-ISSN 1873-3468, Vol. 587, no 21, p. 3480-6Article in journal (Refereed)
    Abstract [en]

    Sdh3/Shh3, a subunit of mitochondrial succinate dehydrogenase, contains transmembrane domains with a hydrophobicity comparable to that of endoplasmic reticulum (ER) proteins. Here, we show that a C-terminal reporter fusion to Sdh3/Shh3 results in partial mis-targeting of the protein to the ER. This mis-targeting is mediated by the signal recognition particle (SRP) and depends on the length of the C-terminal tail. These results imply that if nuclear-encoded mitochondrial proteins contain strongly hydrophobic transmembrane domains and a long C-terminal tail, they have the potential to be recognized by SRP and mis-targeted to the ER.

1 - 13 of 13
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf