Gunnar von Heijne

Gunnar von Heijne

Professor in Biochemistry

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Works at Department of Biochemistry and Biophysics
Telephone 08-16 25 90
Visiting address Arrheniuslaboratoriet, Svante Arrheniusväg 12
Room A 435
Postal address Institutionen för biokemi och biofysik 106 91 Stockholm

About me

PhD in Theoretical Physics, the Royal Institute of Technology, Stockholm, 1980.

Postdoc, Department of Microbiology and Immunology, University of Michigan, Ann Arbor 1980 – 1981.

Assistant Professor, the Royal Institute of Technology, Stockholm, 1981-1988

Science correspondent for the Swedish National Radio (half-time) 1982 - 1985

Associate Professor, Karolinska Institutet, Stockholm, 1989-1994

Professor of Theoretical Chemistry, Stockholm University, 1994-

Director of Stockholm Bioinformatics Center, November 2000 – February 2006

Director of the Center for Biomembrane Research, March 2006 – December 2015

Vice Director, Science for Life Laboratory Stockholm, January 2009 – June 2015

Director of the SciLifeLab National Cryo-EM Facility, January 2016 – present


Membrane protein assembly and structure.

Membrane proteins serve a number of very important functions in both prokaryotic and eukaryotic cells. They are built according to structural principles different from those of globular proteins. A full understanding of membrane proteins requires a conceptual framework where processes of protein translocation across membranes and the physical chemistry of lipid-protein interactions play major roles.

Work in our lab has pointed to the central importance of positively charged amino acids as determinants of membrane protein topology, has led to the development of new theoretical methods for predicting transmembrane segments, and has illuminated many aspects of membrane protein assembly in both prokaryotic and eukaryotic cells. Ongoing work is directed towards a better understanding of the folding and assembly of membrane proteins.


Group members

José Farias, Postdoc

Nir Fluman, Postdoc

Grant Kemp, Postdoc

Renuka Kudva, Postdoc

Ane Metola Martinez, Postdoc

Daphne Mermans, Postdoc

Felix Nicolaus, PhD Student

Hena Sandhu, PhD Student




A selection from Stockholm University publication database
  • 2016. Karin Öjemalm (et al.). Proceedings of the National Academy of Sciences of the United States of America 113 (38), 10559-10564

    Cotranslational translocon-mediated insertion of membrane proteins into the endoplasmic reticulum is a key process in membrane protein biogenesis. Although the mechanism is understood in outline, quantitative data on the energetics of the process is scarce. Here, we have measured the effect on membrane integration efficiency of nonproteinogenic analogs of the positively charged amino acids arginine and lysine incorporated into model transmembrane segments. We provide estimates of the influence on the apparent free energy of membrane integration (Delta G(app)) of snorkeling of charged amino acids toward the lipid-water interface, and of charge neutralization. We further determine the effect of fluorine atoms and backbone hydrogen bonds (H-bonds) on Delta G(app). These results help establish a quantitative basis for our understanding of membrane protein assembly in eukaryotic cells.

  • 2016. Daniela Schibich (et al.). Nature 536 (7615), 219-+

    Signal recognition particle (SRP) is a universally conserved protein-RNA complex that mediates co-translational protein translocation and membrane insertion by targeting translating ribosomes to membrane translocons(1). The existence of parallel co- and post-translational transport pathways(2), however, raises the question of the cellular substrate pool of SRP and the molecular basis of substrate selection. Here we determine the binding sites of bacterial SRP within the nascent proteome of Escherichia coli at amino acid resolution, by sequencing messenger RNA footprints of ribosome-nascent-chain complexes associated with SRP. SRP, on the basis of its strong preference for hydrophobic transmembrane domains (TMDs), constitutes a compartment-specific targeting factor for nascent inner membrane proteins (IMPs) that efficiently excludes signal-sequence-containing precursors of periplasmic and outer membrane proteins. SRP associates with hydrophobic TMDs enriched in consecutive stretches of hydrophobic and bulky aromatic amino acids immediately on their emergence from the ribosomal exit tunnel. By contrast with current models, N-terminal TMDs are frequently skipped and TMDs internal to the polypeptide sequence are selectively recognized. Furthermore, SRP binds several TMDs in many multi-spanning membrane proteins, suggesting cycles of SRP-mediated membrane targeting. SRP-mediated targeting is not accompanied by a transient slowdown of translation and is not influenced by the ribosome-associated chaperone trigger factor (TF), which has a distinct substrate pool and acts at different stages during translation. Overall, our proteome-wide data set of SRP-binding sites reveals the underlying principles of pathway decisions for nascent chains in bacteria, with SRP acting as the dominant triaging factor, sufficient to separate IMPs from substrates of the SecA-SecB post-translational translocation and TF-assisted cytosolic protein folding pathways.

  • 2016. Ola B. Nilsson (et al.). Journal of Molecular Biology 428 (6), 1356-1364

    Cotranslational protein folding can generate pulling forces on the nascent chain that can affect the instantaneous translation rate and thereby possibly feed back on the folding process. Such feedback would represent a new way of coupling translation and folding, different from coupling based on, for example, codon usage. However, to date, we have carried out the experiments used to measure pulling forces generated by cotranslational protein folding either in reconstituted in vitro translation systems lacking chaperones, in ill-defined cell lysates, or in vivo; hence, the effects of chaperones on force generation by folding are unknown. Here, we have studied the cotranslational folding of dihydrofolate reductase (DHFR) in the absence and in the presence of the chaperones trigger factor (TF) and GroEL/ES. DHFR was tethered to the ribosome via a C-terminal linker of varying length, ending with the SecM translational arrest peptide that serves as an intrinsic force sensor reporting on the force generated on the nascent chain when DHFR folds. We find that DHFR folds into its native structure only when it has emerged fully outside the ribosome and that TF and GroEL alone substantially reduces the force generated on the nascent chain by the folding of DHFR, while GroEL/ES has no effect. TF therefore weakens the possible coupling between cotranslational folding and translation.

  • 2015. Nurzian Ismail (et al.). Nature Structural & Molecular Biology 22 (2), 145-149

    On average, every fifth residue in secretory proteins carries either a positive or a negative charge. In a bacterium such as Escherichia coli, charged residues are exposed to an electric field as they transit through the inner membrane, and this should generate a fluctuating electric force on a translocating nascent chain. Here, we have used translational arrest peptides as in vivo force sensors to measure this electric force during cotranslational chain translocation through the SecYEG translocon. We find that charged residues experience a biphasic electric force as they move across the membrane, including an early component with a maximum when they are 47-49 residues away from the ribosomal P site, followed by a more slowly varying component. The early component is generated by the transmembrane electric potential, whereas the second may reflect interactions between charged residues and the periplasmic membrane surface.

  • 2015. Ola B. Nilsson (et al.). Cell reports 12 (10), 1533-1540

    At what point during translation do proteins fold? It is well established that proteins can fold cotranslationally outside the ribosome exit tunnel, whereas studies of folding inside the exit tunnel have so far detected only the formation of helical secondary structure and collapsed or partially structured folding intermediates. Here, using a combination of co-translational nascent chain force measurements, inter-subunit fluorescence resonance energy transfer studies on single translating ribosomes, molecular dynamics simulations, and cryoelectron microscopy, we show that a small zinc-finger domain protein can fold deep inside the vestibule of the ribosome exit tunnel. Thus, for small protein domains, the ribosome itself can provide the kind of sheltered folding environment that chaperones provide for larger proteins.

  • 2015. Florian Cymer (et al.). Journal of Biological Chemistry 290 (16), 10208-10215

    Translational arrest peptides (APs) are short stretches of polypeptides that induce translational stalling when synthesized on a ribosome. Mechanical pulling forces acting on the nascent chain can weaken or even abolish stalling. APs can therefore be used as in vivo force sensors, making it possible to measure the forces that act on a nascent chain during translation with single-residue resolution. It is also possible to score the relative strengths of APs by subjecting them to a given pulling force and ranking them according to stalling efficiency. Using the latter approach, we now report an extensive mutagenesis scan of a strong mutant variant of the Mannheimia succiniciproducens SecM AP and identify mutations that further increase the stalling efficiency. Combining three such mutations, we designed an AP that withstands the strongest pulling force we are able to generate at present. We further show that diproline stretches in a nascent protein act as very strong APs when translation is carried out in the absence of elongation factor P. Our findings highlight critical residues in APs, show that certain amino acid sequences induce very strong translational arrest and provide a toolbox of APs of varying strengths that can be used for in vivo force measurements.

  • 2012. Nurzian Ismail (et al.). Nature Structural & Molecular Biology 19 (10), 1018-1022

    Membrane proteins destined for insertion into the inner membrane of bacteria or the endoplasmic reticulum membrane in eukaryotic cells are synthesized by ribosomes bound to the bacterial SecYEG or the homologous eukaryotic Sec61 translocon. During co-translational membrane integration, transmembrane alpha-helical segments in the nascent chain exit the translocon through a lateral gate that opens toward the surrounding membrane, but the mechanism of lateral exit is not well understood. In particular, little is known about how a transmembrane helix behaves when entering and exiting the translocon. Using translation-arrest peptides from bacterial SecM proteins and from the mammalian Xbp1 protein as force sensors, we show that substantial force is exerted on a transmembrane helix at two distinct points during its transit through the translocon channel, providing direct insight into the dynamics of membrane integration.

Show all publications by Gunnar von Heijne at Stockholm University

Last updated: August 1, 2019

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