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Apolar surface area determines the efficiency of translocon-mediated membrane-protein integration into the endoplasmic reticulum
Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
Stockholm University, Faculty of Science, Department of Neurochemistry.
Stockholm University, Faculty of Science, Department of Neurochemistry.ORCID iD: 0000-0001-6107-0844
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2011 (English)In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 108, no 31, E359-E364 p.Article in journal (Refereed) Published
Abstract [en]

Integral membrane proteins are integrated cotranslationally into the membrane of the endoplasmic reticulum in a process mediated by the Sec61 translocon. Transmembrane α-helices in a translocating polypeptide chain gain access to the surrounding membrane through a lateral gate in the wall of the translocon channel [van den Berg B, et al. (2004) Nature427:36–44; Zimmer J, et al. (2008) Nature455:936–943; Egea PF, Stroud RM (2010)Proc Natl Acad Sci USA 107:17182–17187]. To clarify the nature of the membrane-integration process, we have measured the insertion efficiency into the endoplasmic reticulum membrane of model hydrophobic segments containing nonproteinogenic aliphatic and aromatic amino acids. We find that an amino acid’s contribution to the apparent free energy of membrane-insertion is directly proportional to the nonpolar accessible surface area of its side chain, as expected for thermodynamic partitioning between aqueous and nonpolar phases. But unlike bulk-phase partitioning, characterized by a nonpolar solvation parameter of 23 cal∕ðmol · Å2Þ, the solvation parameter for transfer from translocon to bilayer is 6 –10 cal∕ðmol · Å2Þ, pointing to important differences between translocon-guided partitioning and simple water-to-membrane partitioning. Our results provide compelling evidence for a termodynamic partitioning model and insights into the physical properties of the translocon.

Place, publisher, year, edition, pages
2011. Vol. 108, no 31, E359-E364 p.
Keyword [en]
flexizyme, hydrophobicity, nonproteinogenic amino acid
National Category
Chemical Sciences Biochemistry and Molecular Biology
Research subject
Neurochemistry with Molecular Neurobiology; Biochemistry
URN: urn:nbn:se:su:diva-71400DOI: 10.1073/pnas.1100120108ISI: 000293385700008PubMedID: 21606334OAI: diva2:484820
Swedish Research Council
Available from: 2012-01-27 Created: 2012-01-27 Last updated: 2016-02-23Bibliographically approved
In thesis
1. Membrane protein topogenesis
Open this publication in new window or tab >>Membrane protein topogenesis
2015 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The membranes of cells are highly complex and heterogeneous structures that fulfill multiple vital tasks. They form thin barriers that seal out the environment, thus defining the cell’s boundaries. They mediate the selective exchange of information and substances between the inside and outside of cells, thus making cellular life and survival possible and allowing fast adaptation to changing conditions. Not least importantly, they harbor key components of many essential processes such as the photosynthesis and respiration. Membranes are composed of a largely apolar lipid matrix densely punctuated with a large number of different proteins. These so-called membrane proteins usually span the lipid matrix and protrude out into the space on either side of the membrane.

Over millions of years of evolution, cells have developed an incredible machinery to facilitate the insertion of membrane proteins into the membrane. Our understanding of these machines and the insertion processes they mediate has reached a point where we have a very good picture of membrane protein biogenesis in various types of cells. However, more data still needs to be collected to completely comprehend the complex molecular mechanisms and the physical chemistry that underlies the different insertion processes.

The work presented in this thesis contributes to that understanding. More precisely, we have studied how weakly hydrophobic transmembrane elements of membrane proteins, which cannot spontaneously enter the largely apolar membrane matrices, are efficiently incorporated. Indeed, such elements are quite common in membrane proteins and our work has lead to the formulation of a novel mechanism for how they can be integrated into biological membranes.

We have also added to the understanding of the physical chemistry that underlies the membrane insertion process by systematically introducing non-proteinogenic amino acids into a membrane-spanning segment of a membrane protein and studying its membrane insertion capability.

Place, publisher, year, edition, pages
Stockholm: Department of Biochemistry and Biophysics, Stockholm University, 2015. 69 p.
National Category
Biochemistry and Molecular Biology
Research subject
urn:nbn:se:su:diva-113384 (URN)978-91-7649-089-1 (ISBN)
Public defence
2015-03-09, Magnélisalen, Kemiska övningslaboratoriet, Svante Arrhenius väg 16 B, Stockholm, 10:00 (English)
Available from: 2015-02-15 Created: 2015-01-29 Last updated: 2015-03-11Bibliographically approved

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Öjemalm, KarinLangel, ÜloNilsson, IngMarievon Heijne, Gunnar
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