title: Canonical azimuthal rotations and flanking residues constrain the orientation of transmembrane helices.
abstract: In biological membranes the alignment of embedded proteins provides crucial structural information. The transmembrane (TM) parts have well-defined secondary structures, in most cases α-helices and their orientation is given by a tilt angle and an azimuthal rotation angle around the main axis. The tilt angle is readily visualized and has been found to be functionally relevant. However, there exist no general concepts on the corresponding azimuthal rotation. Here, we show that TM helices prefer discrete rotation angles. They arise from a combination of intrinsic properties of the helix geometry plus the influence of the position and type of flanking residues at both ends of the hydrophobic core. The helical geometry gives rise to canonical azimuthal angles for which the side chains of residues from the two ends of the TM helix tend to have maximum or minimum immersion within the membrane. This affects the preferential position of residues that fall near hydrophobic/polar interfaces of the membrane, depending on their hydrophobicity and capacity to form specific anchoring interactions. On this basis, we can explain the orientation and dynamics of TM helices and make accurate predictions, which correspond well to the experimental values of several model peptides (including dimers), and TM segments of polytopic membrane proteins.
authors.affiliation: Institute of Molecular Science, University of Valencia, Paterna (Valencia), Spain.
authors.forename: Orlando L
authors.initials: OL
authors.lastname: Sánchez-Muñoz
authors.forename: Erik
authors.initials: E
authors.lastname: Strandberg
authors.forename: E
authors.initials: E
authors.lastname: Esteban-Martín
authors.forename: Stephan L
authors.initials: SL
authors.lastname: Grage
authors.forename: Anne S
authors.initials: AS
authors.lastname: Ulrich
authors.forename: Jesús
authors.initials: J
authors.lastname: Salgado
mesh_terms: D000595:Amino Acid Sequence; D002462:Cell Membrane; D008565:Membrane Proteins / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry; D015221:Potassium Channels / Q000737:chemistry; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D012399:Rotation
chemical_list: D008565:Membrane Proteins; D010446:Peptide Fragments; D015221:Potassium Channels
references.citation: Biochemistry. 2001 Jun 5;40(22):6553-8
references.pmid: 11380249
references.citation: Biophys J. 2007 Dec 15;93(12):4278-88
references.pmid: 17720729
references.citation: Biochemistry. 2007 Jun 26;46(25):7514-24
references.pmid: 17530863
references.citation: PLoS Comput Biol. 2010 Mar 19;6(3):e1000714
references.pmid: 20333233
references.citation: Biochim Biophys Acta. 1998 Dec 8;1429(1):113-28
references.pmid: 9920390
references.citation: Eur Biophys J. 2012 May;41(5):475-82
references.pmid: 22453992
references.citation: Annu Rev Biochem. 2007;76:125-40
references.pmid: 17579561
references.citation: Biophys J. 2012 Sep 19;103(6):1227-35
references.pmid: 22995495
references.citation: Biophys J. 2010 Sep 8;99(5):1455-64
references.pmid: 20816057
references.citation: Biochemistry. 2009 Dec 8;48(48):11441-8
references.pmid: 19860438
references.citation: Biophys J. 2011 Feb 2;100(3):656-664
references.pmid: 21281580
references.citation: J Biol Chem. 2010 Oct 8;285(41):31723-30
references.pmid: 20667827
references.citation: Trends Biochem Sci. 1999 Sep;24(9):364-7
references.pmid: 10470037
references.citation: J Magn Reson. 2000 May;144(1):162-7
references.pmid: 10783287
references.citation: Biophys J. 2006 Apr 1;90(7):2326-43
references.pmid: 16428278
references.citation: Biophys J. 2005 Apr;88(4):2626-37
references.pmid: 15665131
references.citation: Biophys J. 2010 May 19;98(9):1864-72
references.pmid: 20441750
references.citation: Biochemistry. 2003 May 13;42(18):5341-8
references.pmid: 12731875
references.citation: J Am Chem Soc. 2007 Dec 12;129(49):15174-81
references.pmid: 18001020
references.citation: J Mol Graph. 1996 Feb;14(1):33-8, 27-8
references.pmid: 8744570
references.citation: Bioinformatics. 2009 Apr 15;25(8):996-1003
references.pmid: 19244388
references.citation: Biochemistry. 2012 Mar 13;51(10):2044-53
references.pmid: 22364236
references.citation: Nature. 2005 Dec 1;438(7068):581-9
references.pmid: 16319877
references.citation: Proteins. 2006 Mar 1;62(4):1010-25
references.pmid: 16372357
references.citation: Physiol Rev. 2001 Apr;81(2):685-740
references.pmid: 11274342
references.citation: Biophys J. 2011 Jun 22;100(12):2922-8
references.pmid: 21689525
references.citation: Proc Natl Acad Sci U S A. 2012 Jun 12;109(24):E1540-7
references.pmid: 22645369
references.citation: Biochemistry. 2005 Jan 25;44(3):1004-12
references.pmid: 15654757
references.citation: Biochemistry. 1996 Jan 23;35(3):1037-45
references.pmid: 8547239
references.citation: J Magn Reson. 2000 May;144(1):150-5
references.pmid: 10783285
references.citation: J Biol Chem. 1999 Jul 23;274(30):20839-46
references.pmid: 10409625
references.citation: Science. 1997 Apr 4;276(5309):131-3
references.pmid: 9082985
references.citation: Biophys J. 2011 Dec 21;101(12):2939-47
references.pmid: 22208192
references.citation: Biophys J. 2002 Sep;83(3):1479-88
references.pmid: 12202373
references.citation: Biochim Biophys Acta. 2012 May;1818(5):1242-9
references.pmid: 22326890
references.citation: Proc Natl Acad Sci U S A. 2009 Apr 21;106(16):6644-9
references.pmid: 19346472
references.citation: Proteins. 2009 Mar;74(4):857-71
references.pmid: 18704938
references.citation: Biophys J. 2009 Apr 22;96(8):3223-32
references.pmid: 19383466
references.citation: J Mol Biol. 2004 May 28;339(2):471-9
references.pmid: 15136048
references.citation: Biophys J. 2004 Jun;86(6):3709-21
references.pmid: 15189867
references.citation: Proc Natl Acad Sci U S A. 2009 Feb 3;106(5):1409-14
references.pmid: 19190187
references.citation: Biophys J. 2008 May 15;94(10):3996-4013
references.pmid: 18234817