Effect of flanking residues on the conformational sampling of the internal fusion peptide from Ebola virus.
Fusion peptides mediate viral and host-cell membrane fusion during viral entry. The monomeric form of the internal fusion peptide from Ebola virus was studied in membrane bilayer and water environments with computer simulations using replica exchange sampling and an implicit solvent description of the environment. Wild-type Ebola fusion peptide (EFP), the W8A mutant form, and an extended construct with flanking residues were examined. It was found that the monomeric form of wild-type EFP adopts coil-helix-coil structure with a short helix from residues 8 to 11 mostly sampling orientations parallel to the membrane surface. W8A mutation disrupts the helicity in the N-terminal region of the peptide and leads to a preference for slightly oblique orientation relative to the membrane surface. The addition of flanking residues also alters the fusion peptide conformation with either a helix-break-helix structure or extended N and C-termini and reduced membrane insertion. In water, the fusion peptide is found to adopt structures with low helicity.
Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, Michigan 48824, USA.
Adam J
AJ
Jaskierny
Afra
A
Panahi
Michael
M
Feig
D000595:Amino Acid Sequence; D029043:Ebolavirus / Q000737:chemistry* / Q000378:metabolism; D054884:Host-Pathogen Interactions; D008051:Lipid Bilayers; D056004:Molecular Dynamics Simulation; D009154:Mutation; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism; D011487:Protein Conformation; D020539:Sequence Analysis, Protein; D014760:Viral Fusion Proteins / Q000737:chemistry* / Q000378:metabolism
D008051:Lipid Bilayers; D010455:Peptides; D014760:Viral Fusion Proteins
Nature. 1981 Jan 29;289(5796):366-73
7464906
J Biol Chem. 2006 Mar 3;281(9):5760-70
16407195
J Am Chem Soc. 2009 Sep 23;131(37):13228-9
19711890
J Comput Chem. 2009 Jul 30;30(10):1545-614
19444816
Arch Virol Suppl. 1993;7:81-100
8219816
J Comput Chem. 2006 Apr 30;27(6):719-29
16518883
J Virol. 1998 Mar;72(3):1775-81
9499027
J Chem Theory Comput. 2007 Sep;3(5):1734-48
26627618
Proc Natl Acad Sci U S A. 1999 Mar 16;96(6):2662-7
10077567
J Phys Chem B. 2006 Aug 31;110(34):17240-51
16928023
Proc Natl Acad Sci U S A. 2010 Jun 22;107(25):11341-6
20534508
FEBS Lett. 2003 Jan 30;535(1-3):23-8
12560072
J Biol Chem. 2007 Sep 14;282(37):27306-27314
17545161
Virology. 2003 Jun 5;310(2):319-32
12781719
J Chem Phys. 2005 Mar 22;122(12):124706
15836408
Proc Natl Acad Sci U S A. 2001 Jul 17;98(15):8502-6
11447278
Biophys J. 2003 Nov;85(5):2900-18
14581194
Biophys J. 2010 Mar 3;98(5):805-14
20197034
J Virol. 1999 Oct;73(10):8907-12
10482652
J Am Chem Soc. 2006 Mar 22;128(11):3728-36
16536547
Curr Opin Struct Biol. 1999 Apr;9(2):177-83
10322208
J Mol Graph Model. 2004 May;22(5):377-95
15099834
J Comput Chem. 2003 Aug;24(11):1348-56
12827676
Biochim Biophys Acta. 2007 Jan;1768(1):30-8
16999933
FEBS Lett. 2004 Jul 2;569(1-3):261-6
15225645
J Mol Biol. 2004 Jan 9;335(2):631-40
14672669
J Phys Chem B. 2006 Jan 12;110(1):548-56
16471567
J Phys Chem B. 2010 Jan 28;114(3):1407-16
20043654
Biochim Biophys Acta. 2003 Jan 10;1609(1):45-54
12507757
Biophys J. 2001 Feb;80(2):643-55
11159433
J Chem Phys. 2004 Jan 8;120(2):903-11
15267926
J Am Chem Soc. 2004 Jan 28;126(3):698-9
14733527
Cell. 2001 Apr 6;105(1):137-48
11301009