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Membrane topology of the human seipin protein
Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
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2006 (English)In: FEBS Letters, ISSN 0014-5793, E-ISSN 1873-3468, Vol. 580, no 9, 2281-2284 p.Article in journal (Refereed) Published
Abstract [en]

The Berardinelli-Seip congenital lipodystrophy type 2 (BSCL2) gene encodes an integral membrane protein, called seipin, of unknown function localized to the endoplasmic reticulum of eukaryotic cells. Seipin is associated with the heterogeneous genetic disease BSCL2, and mutations in an N-glycosylation motif links the protein to two other disorders, autosomal-dominant distal hereditary motor neuropathy type V and Silver syndrome. Here, we report a topological study of seipin using an in vitro topology mapping assay. Our results suggest that the predominant form of seipin is 462 residues long and has an N-cyt-C-cyt orientation with a long luminal loop between the two transmembrane helices.

Place, publisher, year, edition, pages
2006. Vol. 580, no 9, 2281-2284 p.
Keyword [en]
seipin, N-linked glycosylation, oligosaccharyl transferase, topology mapping, BCSL gene
National Category
Biological Sciences
URN: urn:nbn:se:su:diva-25793DOI: 10.1016/j.febslet.2006.03.040ISI: 000237012800021OAI: diva2:200525
Available from: 2009-03-19 Created: 2009-02-20 Last updated: 2016-02-24Bibliographically approved
In thesis
1. Integration and topology of membrane proteins
Open this publication in new window or tab >>Integration and topology of membrane proteins
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Membrane proteins comprise around 20-30% of most proteomes. They play important roles in most biochemical pathways. All receptors and ion channels are membrane proteins, which make them attractive targets for drug design. Membrane proteins insert and fold co-translationally into the endoplasmic reticular membrane of eukaryotic cells. The protein-conducting channel that inserts the protein into the membrane is called Sec61 translocon, which is a hetero-oligomeric channel that allows transmembrane segments to insert laterally into the lipid bilayer. The focus of this thesis is how the translocon recognizes the transmembrane helices and integrates them into the membrane.

We have investigated the sequence requirements for the translocon-mediated integration of a transmembrane α-helix into the ER by challenging the Sec61 translocon with designed polypeptide segments in an in vitro expression system that allows a quantitative assessment of membrane insertion efficiency. Our studies suggest that helices might interact with each other already during the membrane-insertion step, possibly forming helical hairpins that partition into the membrane as a single unit. Further, the insertion efficiency for Nin-Cout vs. Nout-Cin transmembrane helices and the integration efficiency of Alzheimer’s Aβ-peptide fragments has been investigated.

Finally, detailed topology mapping was performed on two biologically interesting proteins with unknown topology, the human seipin protein and Drosophila melanogaster odorant receptor OR83b.

Place, publisher, year, edition, pages
Stockholm: Institutionen för biokemi och biofysik, 2009. 53 p.
insertion, Sec61, translocation
National Category
Biochemistry and Molecular Biology
Research subject
urn:nbn:se:su:diva-8575 (URN)978-91-7155-827-5 (ISBN)
Public defence
2009-04-09, Magnélisalen, Kemiska övningslaboratoriet, Svante Arrhenius väg 12 A, Stockholm, 10:00 (English)
Available from: 2009-03-12 Created: 2009-02-20 Last updated: 2016-02-23Bibliographically approved

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von Heijne, GunnarNilsson, IngMarie
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