Gunnar von Heijne | Stockholm University (original) (raw)

Papers by Gunnar von Heijne

Research paper thumbnail of How hydrophobic is alanine?

Abstract By a number of measures, alanine is poised at the threshold between those amino acids th... more Abstract By a number of measures, alanine is poised at the threshold between those amino acids that promote the membrane integration of transmembrane α-helices and those that do not.

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Research paper thumbnail of Translocation of anthrax toxin: Lord of the rings

Summary [HN11] Many microorganisms have evolved ingenious ways of shipping toxic proteins into ta... more Summary [HN11] Many microorganisms have evolved ingenious ways of shipping toxic proteins into target cells. In his Perspective, von Heijne discusses a study by Krantz et al. that reveals how anthrax toxin gets into a cell. A ring of aromatic amino acids in a pore formed by anthrax toxin helps unfold other anthrax toxin proteins and facilitate their translocation across the cell membrane.

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Research paper thumbnail of On the Emergence of New Function in PrimitiveiBrote

The problem of creating proteins with new functions out of already existing proteins is treated i... more The problem of creating proteins with new functions out of already existing proteins is treated in some detail. It is shown that the generally accepted process of a gene-duplication followed by random mutational events should have been inefficient as a means of evolution in primitive cells. An alternative scheme, based on considerations of protein folding processes, is presented, and is shown, by the means of a specific example, to give a consistent picture of the evolution of primitive proteins with new functions.

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Research paper thumbnail of Formation of transmembrane helices in vivo—is hydrophobicity all that matters?

Membrane Protein Insertion into the ER While the insertion of a hydrophobic membrane protein into... more Membrane Protein Insertion into the ER While the insertion of a hydrophobic membrane protein into a biological membrane might appear to be a simple question of partitioning from water into a lipid bilayer, this is not how it works in a cell.

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Research paper thumbnail of The DsbA-DsbB system affects the formation of disulfide bonds in periplasmic but not in intramembraneous protein domains

Abstract The DsbA and DsbB proteins of Escherichia coli are involved in facilitating the formatio... more Abstract The DsbA and DsbB proteins of Escherichia coli are involved in facilitating the formation of disulfide bonds in periplasmic proteins. Here, we show that the rate of formation of a disulfide bond in the periplasmic domain of the inner membrane protein leader peptidase is reduced in dsbA and dsbB strains, whereas the rate of formation of a disulfide bond engineered into the membrane embedded domain of the same protein is completely unaffected by these mutations.

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Research paper thumbnail of The membrane protein universe: what's out there and why bother?

Abstract. Chances are that you have come across membrane proteins many times in your professional... more Abstract. Chances are that you have come across membrane proteins many times in your professional life: ion channels, aquaporins, G-protein-coupled receptors, drug resistance proteins. But it is also quite likely that you have never bothered to think about what the implications are of being a membrane protein, as opposed to a soluble protein. What is special about membrane proteins in terms of structure and function, how many membrane proteins are out there, how are they made in the cell?

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Research paper thumbnail of A day in the life of Dr K. or how I learned to stop worrying and love lysozyme: a tragedy in six acts

About the play: In modern drama, the agonizing nature of membrane protein work has not been adequ... more About the play: In modern drama, the agonizing nature of membrane protein work has not been adequately acknowledged.

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Research paper thumbnail of Helix-helix packing in a membrane-like environment

The unique ability of the glycophorin A transmembrane helix to dimerize in SDS has previously bee... more The unique ability of the glycophorin A transmembrane helix to dimerize in SDS has previously been exploited in studies of the sequence specificity of helix-helix packing in a micellar environment. Here, we have made different insertion mutants in the critical helix-helix interface segment, and find that efficient dimerization can be mediated by a wider range of sequence motifs than suggested by the earlier studies.

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Research paper thumbnail of Membrane protein structural biology-How far can the bugs take us?(Review)

Membrane proteins are core components of many essential cellular processes, and high-resolution s... more Membrane proteins are core components of many essential cellular processes, and high-resolution structural data is therefore highly sought after. However, owing to the many bottlenecks associated with membrane protein crystallization, progress has been slow. One major problem is our inability to obtain sufficient quantities of membrane proteins for crystallization trials. Traditionally, membrane proteins have been isolated from natural sources, or for prokaryotic proteins, expressed by recombinant techniques.

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Research paper thumbnail of Forces involved in the assembly and stabilization of membrane proteins.

Abstract Hydrophobic organization: Determination of the structure of the bacterial photosynthetic... more Abstract Hydrophobic organization: Determination of the structure of the bacterial photosynthetic reaction center, bacterial porins, and bacteriorhodopsin allows a comparison of the basic structural features of integral membrane proteins. Structure parameters of membrane-and water-soluble proteins are surprisingly similar, given the different dielectric environments, except for the polarity of residues on the protein surface.

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Research paper thumbnail of Position-specific Asp-Lys pairing can affect signal sequence function and membrane protein topology.

Abstract Positively charged amino acids are major determinants of the topology of bacterial inner... more Abstract Positively charged amino acids are major determinants of the topology of bacterial inner membrane proteins, whereas negatively charged residues by themselves have little or no influence on the transmembrane orientation. Further, positively charged amino acids can very efficiently block the function of signal sequences when placed immediately downstream, while negatively charged residues are much less potent also in this regard.

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Research paper thumbnail of Ala‐insertion scanning mutagenesis of the glycophorin a transmembrane helix: A rapid way to map helix‐helix interactions in integral membrane proteins

Abstract Alanine insertions into the glycophorin A transmembrane helix are found to disrupt helix... more Abstract Alanine insertions into the glycophorin A transmembrane helix are found to disrupt helix-helix dimerization in a way that is fully consistent with earlier saturation mutagenesis data, suggesting that Ala-insertion scanning can be used to rapidly map the approximate location of structurally and/or functionally important segments in transmembrane helices.

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Research paper thumbnail of Insertion of a bacterial secondary transport protein in the endoplasmic reticulum membrane

Abstract The sodium ion-dependent citrate carrier of Klebsiella pneumoniae (CitS) contains 12 hyd... more Abstract The sodium ion-dependent citrate carrier of Klebsiella pneumoniae (CitS) contains 12 hydrophobic potential transmembrane domains. Surprisingly, an alkaline phosphatase fusion study in Escherichia coli has suggested that only 9 of these domains are embedded in the membrane, and 3 are translocated to the periplasm (van Geest, M., and Lolkema, JS (1996) J. Biol. Chem. 271, 25582–25589).

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Research paper thumbnail of Different conformations of nascent polypeptides during translocation across the ER membrane

Background In eukaryotic cells, proteins are translocated across the ER membrane through a contin... more Background In eukaryotic cells, proteins are translocated across the ER membrane through a continuous ribosome-translocon channel. It is unclear to what extent proteins can fold already within the ribosome-translocon channel, and previous studies suggest that only a limited degree of folding (such as the formation of isolated α-helices) may be possible within the ribosome.

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Research paper thumbnail of Inhibition of protein translocation across the endoplasmic reticulum membrane by sterols

Abstract Cholesterol and related sterols are known to modulate the physical properties of biologi... more Abstract Cholesterol and related sterols are known to modulate the physical properties of biological membranes and can affect the activities of membrane-bound protein complexes. Here, we report that an early step in protein translocation across the endoplasmic reticulum (ER) membrane is reversibly inhibited by cholesterol levels significantly lower than those found in the plasma membrane.

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Research paper thumbnail of A turn propensity scale for transmembrane helices

The formation of tight turns in globular proteins has been studied for decades, both experimental... more The formation of tight turns in globular proteins has been studied for decades, both experimentally and by statistical analysis of known structures, and reliable turn propensity scales have been established (Creighto n, 1993; von Heijne, 1987). Remarkably, however, essentially nothing is known about the residue characteristics responsible for the formation of tight turns between transmembrane α-helices in integral membrane proteins.

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Research paper thumbnail of Do protein–lipid interactions determine the recognition of transmembrane helices at the ER translocon?

Abstract Membrane-protein integration, folding and assembly processes in vivo depend on complex t... more Abstract Membrane-protein integration, folding and assembly processes in vivo depend on complex targeting, translocation, chaperoning, and sorting machineries that somehow read the 'molecular code'built into the nascent polypeptide, ultimately producing a properly folded protein integrated into the correct target membrane.

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Research paper thumbnail of Membrane protein topology: effects of delta mu H+ on the translocation of charged residues explain the'positive inside'rule.

Abstract The membrane electrochemical potential is critical for the export of most periplasmic pr... more Abstract The membrane electrochemical potential is critical for the export of most periplasmic proteins in Escherichia coli. Its exact role during insertion of integral inner membrane proteins, however, remains obscure.

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Research paper thumbnail of Recent advances in membrane biochemistry

Abstract This Biochemical Society Annual Symposium on Recent Advances in Membrane Biochemistry wa... more Abstract This Biochemical Society Annual Symposium on Recent Advances in Membrane Biochemistry was organized to bring together experts from across the spectrum of biomembrane disciplines from the biological to the biophysical/structural, with the intention of promoting interactions and collaborations across the field.

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Research paper thumbnail of Architecture of helix bundle membrane proteins: an analysis of cytochrome c oxidase from bovine mitochondria

Abstract We have analyzed the structure of mitochondrial cytochrome c oxidase in terms of general... more Abstract We have analyzed the structure of mitochondrial cytochrome c oxidase in terms of general characteristics thought to be important for describing the architecture of helix bundle membrane proteins. Many aspects of the structure are similar to what has previously been found for the photosynthetic reaction center and bacteriorhodopsin. Our results lead to a considerably more precise general picture of membrane protein architecture than has hitherto been possible to obtain.

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Research paper thumbnail of How hydrophobic is alanine?

Abstract By a number of measures, alanine is poised at the threshold between those amino acids th... more Abstract By a number of measures, alanine is poised at the threshold between those amino acids that promote the membrane integration of transmembrane α-helices and those that do not.

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Research paper thumbnail of Translocation of anthrax toxin: Lord of the rings

Summary [HN11] Many microorganisms have evolved ingenious ways of shipping toxic proteins into ta... more Summary [HN11] Many microorganisms have evolved ingenious ways of shipping toxic proteins into target cells. In his Perspective, von Heijne discusses a study by Krantz et al. that reveals how anthrax toxin gets into a cell. A ring of aromatic amino acids in a pore formed by anthrax toxin helps unfold other anthrax toxin proteins and facilitate their translocation across the cell membrane.

Bookmarks Related papers MentionsView impact

Research paper thumbnail of On the Emergence of New Function in PrimitiveiBrote

The problem of creating proteins with new functions out of already existing proteins is treated i... more The problem of creating proteins with new functions out of already existing proteins is treated in some detail. It is shown that the generally accepted process of a gene-duplication followed by random mutational events should have been inefficient as a means of evolution in primitive cells. An alternative scheme, based on considerations of protein folding processes, is presented, and is shown, by the means of a specific example, to give a consistent picture of the evolution of primitive proteins with new functions.

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Formation of transmembrane helices in vivo—is hydrophobicity all that matters?

Membrane Protein Insertion into the ER While the insertion of a hydrophobic membrane protein into... more Membrane Protein Insertion into the ER While the insertion of a hydrophobic membrane protein into a biological membrane might appear to be a simple question of partitioning from water into a lipid bilayer, this is not how it works in a cell.

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Research paper thumbnail of The DsbA-DsbB system affects the formation of disulfide bonds in periplasmic but not in intramembraneous protein domains

Abstract The DsbA and DsbB proteins of Escherichia coli are involved in facilitating the formatio... more Abstract The DsbA and DsbB proteins of Escherichia coli are involved in facilitating the formation of disulfide bonds in periplasmic proteins. Here, we show that the rate of formation of a disulfide bond in the periplasmic domain of the inner membrane protein leader peptidase is reduced in dsbA and dsbB strains, whereas the rate of formation of a disulfide bond engineered into the membrane embedded domain of the same protein is completely unaffected by these mutations.

Bookmarks Related papers MentionsView impact

Research paper thumbnail of The membrane protein universe: what's out there and why bother?

Abstract. Chances are that you have come across membrane proteins many times in your professional... more Abstract. Chances are that you have come across membrane proteins many times in your professional life: ion channels, aquaporins, G-protein-coupled receptors, drug resistance proteins. But it is also quite likely that you have never bothered to think about what the implications are of being a membrane protein, as opposed to a soluble protein. What is special about membrane proteins in terms of structure and function, how many membrane proteins are out there, how are they made in the cell?

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Research paper thumbnail of A day in the life of Dr K. or how I learned to stop worrying and love lysozyme: a tragedy in six acts

About the play: In modern drama, the agonizing nature of membrane protein work has not been adequ... more About the play: In modern drama, the agonizing nature of membrane protein work has not been adequately acknowledged.

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Research paper thumbnail of Helix-helix packing in a membrane-like environment

The unique ability of the glycophorin A transmembrane helix to dimerize in SDS has previously bee... more The unique ability of the glycophorin A transmembrane helix to dimerize in SDS has previously been exploited in studies of the sequence specificity of helix-helix packing in a micellar environment. Here, we have made different insertion mutants in the critical helix-helix interface segment, and find that efficient dimerization can be mediated by a wider range of sequence motifs than suggested by the earlier studies.

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Membrane protein structural biology-How far can the bugs take us?(Review)

Membrane proteins are core components of many essential cellular processes, and high-resolution s... more Membrane proteins are core components of many essential cellular processes, and high-resolution structural data is therefore highly sought after. However, owing to the many bottlenecks associated with membrane protein crystallization, progress has been slow. One major problem is our inability to obtain sufficient quantities of membrane proteins for crystallization trials. Traditionally, membrane proteins have been isolated from natural sources, or for prokaryotic proteins, expressed by recombinant techniques.

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Forces involved in the assembly and stabilization of membrane proteins.

Abstract Hydrophobic organization: Determination of the structure of the bacterial photosynthetic... more Abstract Hydrophobic organization: Determination of the structure of the bacterial photosynthetic reaction center, bacterial porins, and bacteriorhodopsin allows a comparison of the basic structural features of integral membrane proteins. Structure parameters of membrane-and water-soluble proteins are surprisingly similar, given the different dielectric environments, except for the polarity of residues on the protein surface.

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Position-specific Asp-Lys pairing can affect signal sequence function and membrane protein topology.

Abstract Positively charged amino acids are major determinants of the topology of bacterial inner... more Abstract Positively charged amino acids are major determinants of the topology of bacterial inner membrane proteins, whereas negatively charged residues by themselves have little or no influence on the transmembrane orientation. Further, positively charged amino acids can very efficiently block the function of signal sequences when placed immediately downstream, while negatively charged residues are much less potent also in this regard.

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Ala‐insertion scanning mutagenesis of the glycophorin a transmembrane helix: A rapid way to map helix‐helix interactions in integral membrane proteins

Abstract Alanine insertions into the glycophorin A transmembrane helix are found to disrupt helix... more Abstract Alanine insertions into the glycophorin A transmembrane helix are found to disrupt helix-helix dimerization in a way that is fully consistent with earlier saturation mutagenesis data, suggesting that Ala-insertion scanning can be used to rapidly map the approximate location of structurally and/or functionally important segments in transmembrane helices.

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Insertion of a bacterial secondary transport protein in the endoplasmic reticulum membrane

Abstract The sodium ion-dependent citrate carrier of Klebsiella pneumoniae (CitS) contains 12 hyd... more Abstract The sodium ion-dependent citrate carrier of Klebsiella pneumoniae (CitS) contains 12 hydrophobic potential transmembrane domains. Surprisingly, an alkaline phosphatase fusion study in Escherichia coli has suggested that only 9 of these domains are embedded in the membrane, and 3 are translocated to the periplasm (van Geest, M., and Lolkema, JS (1996) J. Biol. Chem. 271, 25582–25589).

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Research paper thumbnail of Different conformations of nascent polypeptides during translocation across the ER membrane

Background In eukaryotic cells, proteins are translocated across the ER membrane through a contin... more Background In eukaryotic cells, proteins are translocated across the ER membrane through a continuous ribosome-translocon channel. It is unclear to what extent proteins can fold already within the ribosome-translocon channel, and previous studies suggest that only a limited degree of folding (such as the formation of isolated α-helices) may be possible within the ribosome.

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Research paper thumbnail of Inhibition of protein translocation across the endoplasmic reticulum membrane by sterols

Abstract Cholesterol and related sterols are known to modulate the physical properties of biologi... more Abstract Cholesterol and related sterols are known to modulate the physical properties of biological membranes and can affect the activities of membrane-bound protein complexes. Here, we report that an early step in protein translocation across the endoplasmic reticulum (ER) membrane is reversibly inhibited by cholesterol levels significantly lower than those found in the plasma membrane.

Bookmarks Related papers MentionsView impact

Research paper thumbnail of A turn propensity scale for transmembrane helices

The formation of tight turns in globular proteins has been studied for decades, both experimental... more The formation of tight turns in globular proteins has been studied for decades, both experimentally and by statistical analysis of known structures, and reliable turn propensity scales have been established (Creighto n, 1993; von Heijne, 1987). Remarkably, however, essentially nothing is known about the residue characteristics responsible for the formation of tight turns between transmembrane α-helices in integral membrane proteins.

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Do protein–lipid interactions determine the recognition of transmembrane helices at the ER translocon?

Abstract Membrane-protein integration, folding and assembly processes in vivo depend on complex t... more Abstract Membrane-protein integration, folding and assembly processes in vivo depend on complex targeting, translocation, chaperoning, and sorting machineries that somehow read the 'molecular code'built into the nascent polypeptide, ultimately producing a properly folded protein integrated into the correct target membrane.

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Membrane protein topology: effects of delta mu H+ on the translocation of charged residues explain the'positive inside'rule.

Abstract The membrane electrochemical potential is critical for the export of most periplasmic pr... more Abstract The membrane electrochemical potential is critical for the export of most periplasmic proteins in Escherichia coli. Its exact role during insertion of integral inner membrane proteins, however, remains obscure.

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Recent advances in membrane biochemistry

Abstract This Biochemical Society Annual Symposium on Recent Advances in Membrane Biochemistry wa... more Abstract This Biochemical Society Annual Symposium on Recent Advances in Membrane Biochemistry was organized to bring together experts from across the spectrum of biomembrane disciplines from the biological to the biophysical/structural, with the intention of promoting interactions and collaborations across the field.

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Architecture of helix bundle membrane proteins: an analysis of cytochrome c oxidase from bovine mitochondria

Abstract We have analyzed the structure of mitochondrial cytochrome c oxidase in terms of general... more Abstract We have analyzed the structure of mitochondrial cytochrome c oxidase in terms of general characteristics thought to be important for describing the architecture of helix bundle membrane proteins. Many aspects of the structure are similar to what has previously been found for the photosynthetic reaction center and bacteriorhodopsin. Our results lead to a considerably more precise general picture of membrane protein architecture than has hitherto been possible to obtain.

Bookmarks Related papers MentionsView impact