title: Apolar surface area determines the efficiency of translocon-mediated membrane-protein integration into the endoplasmic reticulum.
abstract: 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) Nature 427:36-44; Zimmer J, et al. (2008) Nature 455:936-943; 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/(mol · Å(2)), the solvation parameter for transfer from translocon to bilayer is 6-10 cal/(mol · Å(2)), pointing to important differences between translocon-guided partitioning and simple water-to-membrane partitioning. Our results provide compelling evidence for a thermodynamic partitioning model and insights into the physical properties of the translocon.
authors: Center for Biomembrane Research, Department of Biochemistry and Biophysics, Stockholm University, SE-106 91 Stockholm, Sweden.
authors: Karin
authors: K
authors: Öjemalm
authors: Takashi
authors: T
authors: Higuchi
authors: Yang
authors: Y
authors: Jiang
authors: Ülo
authors: Ü
authors: Langel
authors: IngMarie
authors: I
authors: Nilsson
authors: Stephen H
authors: SH
authors: White
authors: Hiroaki
authors: H
authors: Suga
authors: Gunnar
authors: G
authors: von Heijne
references: Cell. 2000 Jul 21;102(2):233-44
references: 10943843
references: Eur J Biochem. 1998 Feb 1;251(3):821-9
references: 9490057
references: Proc Natl Acad Sci U S A. 2010 Oct 5;107(40):17182-7
references: 20855604
references: Nature. 1986 Jan 16-22;319(6050):199-203
references: 3945310
references: Proc Natl Acad Sci U S A. 1992 May 1;89(9):3770-4
references: 1349170
references: Nature. 2007 Nov 29;450(7170):663-9
references: 18046402
references: Nature. 2004 Jan 1;427(6969):36-44
references: 14661030
references: Nature. 2008 Oct 16;455(7215):988-91
references: 18923527
references: J Mol Biol. 2001 Jan 19;305(3):643-56
references: 11152619
references: Nature. 2007 Dec 13;450(7172):1026-30
references: 18075582
references: Proc Natl Acad Sci U S A. 2010 Oct 12;107(41):17598-603
references: 20876127
references: Mol Biol Cell. 2010 May 15;21(10):1662-70
references: 20357000
references: J Biol Chem. 1996 Mar 22;271(12):6651-7
references: 8636082
references: Protein Sci. 1997 Jun;6(6):1302-7
references: 9194190
references: Nature. 2008 Jul 17;454(7202):358-61
references: 18548004
references: J Mol Biol. 1976 Jul 25;105(1):1-12
references: 994183
references: Proc Natl Acad Sci U S A. 1974 Aug;71(8):2925-7
references: 16578715
references: EMBO J. 2001 Apr 2;20(7):1797-806
references: 11285242
references: J Membr Biol. 2011 Jan;239(1-2):35-48
references: 21127848
references: Mol Gen Genet. 1993 May;239(1-2):251-6
references: 8510652
references: Nat Rev Mol Cell Biol. 2008 Feb;9(2):112-24
references: 18216768
references: Nat Methods. 2006 May;3(5):357-9
references: 16628205
references: J Mol Biol. 2010 Feb 12;396(1):221-9
references: 19931281
references: Nature. 2005 Jan 27;433(7024):377-81
references: 15674282
references: Biochemistry. 1996 Apr 23;35(16):5109-24
references: 8611495
references: Biochemistry. 1998 Oct 20;37(42):14713-8
references: 9778346
references: Nature. 2008 Oct 16;455(7215):936-43
references: 18923516
references: J Biol Chem. 2003 Aug 8;278(32):29389-93
references: 12761228
references: Chem Biol. 2007 Dec;14(12):1315-22
references: 18096500
references: Proc Natl Acad Sci U S A. 2011 Mar 1;108(9):3596-601
references: 21317362
references: Proc Natl Acad Sci U S A. 1977 Oct;74(10):4144-5
references: 16592439
references: Annu Rev Biophys. 2008;37:23-42
references: 18573071
references: J Chem Phys. 2009 May 14;130(18):185101
references: 19449954