Turning of the receptor-binding domains opens up the murine leukaemia virus Env for membrane fusion.
The activity of the membrane fusion protein Env of Moloney mouse leukaemia virus is controlled by isomerization of the disulphide that couples its transmembrane (TM) and surface (SU) subunits. We have arrested Env activation at a stage prior to isomerization by alkylating the active thiol in SU and compared the structure of isomerization-arrested Env with that of native Env. Env trimers of respective form were isolated from solubilized particles by sedimentation and their structures were reconstructed from electron microscopic images of both vitrified and negatively stained samples. We found that the protomeric unit of both trimers formed three protrusions, a top, middle and a lower one. The atomic structure of the receptor-binding domain of SU fitted into the upper protrusion. This was formed similar to a bent finger. Significantly, in native Env the tips of the fingers were directed against each other enclosing a cavity below, whereas they had turned outward in isomerization-arrested Env transforming the cavity into an open well. This might subsequently guide the fusion peptides in extended TM subunits into the target membrane.
Wu
Shang-Rung
SR
Department of Biosciences and Nutrition, Karolinska Institute, Huddinge, Sweden.
Sjöberg
Mathilda
M
Wallin
Michael
M
Lindqvist
Birgitta
B
Ekström
Maria
M
Hebert
Hans
H
Koeck
Philip J B
PJ
Garoff
Henrik
H
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D020285:Cryoelectron Microscopy / Q000379:methods; D015686:Gene Products, env / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology*; D015752:Genes, env; D007091:Image Processing, Computer-Assisted; D009052:Leukemia Virus, Murine / Q000378:metabolism*; D051379:Mice; D008954:Models, Biological; D008958:Models, Molecular; D008968:Molecular Conformation; D011485:Protein Binding / Q000235:genetics; D017434:Protein Structure, Tertiary; D014760:Viral Fusion Proteins / Q000378:metabolism*
D015686:Gene Products, env; D014760:Viral Fusion Proteins
Nature. 1991 Aug 22;352(6337):729-31
1908564
J Virol. 1999 May;73(5):3758-63
10196270
J Virol. 1992 Jul;66(7):4258-64
1318404
J Virol. 1993 Mar;67(3):1310-4
8382297
J Virol. 1993 Apr;67(4):2091-6
8445722
Nature. 1994 Sep 1;371(6492):37-43
8072525
J Virol. 1996 Mar;70(3):1768-74
8627699
Nat Struct Biol. 1996 May;3(5):465-9
8612078
J Virol. 1997 Mar;71(3):2092-9
9032341
Cell. 1997 Apr 18;89(2):263-73
9108481
Nature. 1997 May 22;387(6631):426-30
9163431
Science. 1997 Sep 12;277(5332):1662-6
9287219
J Virol. 1997 Oct;71(10):8073-7
9311907
J Virol. 1997 Nov;71(11):8096-102
9343158
Nature. 1998 Jun 18;393(6686):648-59
9641677
EMBO Rep. 2006 Oct;7(10):1000-5
17016458
J Virol. 2007 Oct;81(19):10506-14
17634228
J Biol Chem. 2007 Dec 14;282(50):36724-35
17940280
J Virol. 2008 Mar;82(5):2358-66
18094169
FASEB J. 2008 Apr;22(4):1179-92
18032634
J Virol. 2006 Oct;80(19):9921-5
16973599
J Virol. 1999 Dec;73(12):10164-72
10559332
J Struct Biol. 1999 Dec 1;128(1):82-97
10600563
Proc Natl Acad Sci U S A. 1999 Apr 13;96(8):4319-24
10200260
J Virol. 2005 Feb;79(3):1678-85
15650193
Nature. 2005 Feb 24;433(7028):834-41
15729334
Proc Natl Acad Sci U S A. 2005 Mar 29;102(13):4729-34
15774580
J Virol. 2005 Nov;79(22):13856-64
16254321
Science. 2005 Nov 11;310(5750):1025-8
16284180
EMBO J. 2005 Dec 7;24(23):4144-53
16292345
EMBO J. 2004 Jan 14;23(1):54-65
14685283
Nature. 1981 Jan 29;289(5796):366-73
7464906
Virology. 1982 Jan 30;116(2):499-516
6175079
Cell. 1989 May 19;57(4):659-66
2541919
Methods Enzymol. 1990;182:477-88
1690330
J Exp Med. 1991 Aug 1;174(2):407-15
1713252
FEBS Lett. 1999 Dec 17;463(3):255-9
10606732
Annu Rev Biochem. 2000;69:531-69
10966468
J Virol. 2001 Apr;75(8):3685-95
11264358
Mol Cell. 2001 Jul;8(1):169-79
11511370
J Virol. 2001 Oct;75(19):9096-105
11533173
J Struct Biol. 2003 Jan;141(1):43-52
12576019
J Virol. 2003 Aug;77(15):8596-601
12857932
J Virol. 1998 Aug;72(8):6537-45
9658097
J Virol. 1998 Dec;72(12):9955-65
9811733
J Virol. 1999 Mar;73(3):1802-8
9971757
Anal Biochem. 1991 Dec;199(2):223-31
1812789