Apolar surface area determines the efficiency of translocon-mediated membrane-protein integration into the endoplasmic reticulum
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
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.
flexizyme, hydrophobicity, nonproteinogenic amino acid
Chemical Sciences Biochemistry and Molecular Biology
Research subject Neurochemistry with Molecular Neurobiology; Biochemistry
IdentifiersURN: urn:nbn:se:su:diva-71400DOI: 10.1073/pnas.1100120108ISI: 000293385700008PubMedID: 21606334OAI: oai:DiVA.org:su-71400DiVA: diva2:484820
FunderSwedish Research Council