Cryo-electron tomographic structure of an immunodeficiency virus envelope complex in situ.
The envelope glycoprotein (Env) complexes of the human and simian immunodeficiency viruses (HIV and SIV, respectively) mediate viral entry and are a target for neutralizing antibodies. The receptor binding surfaces of Env are in large part sterically occluded or conformationally masked prior to receptor binding. Knowledge of the unliganded, trimeric Env structure is key for an understanding of viral entry and immune escape, and for the design of vaccines to elicit neutralizing antibodies. We have used cryo-electron tomography and averaging to obtain the structure of the SIV Env complex prior to fusion. Our result reveals novel details of Env organisation, including tight interaction between monomers in the gp41 trimer, associated with a three-lobed, membrane-distal gp120 trimer. A cavity exists at the gp41-gp120 trimer interface. Our model for the spike structure agrees with previously predicted interactions between gp41 monomers, and furthers our understanding of gp120 interactions within an intact spike.
Zanetti
Giulia
G
University of Oxford, Division of Structural Biology, Wellcome Trust Centre for Human Genetics, Henry Wellcome Building for Genomic Medicine, Headington, United Kingdom.
Briggs
John A G
JA
Grünewald
Kay
K
Sattentau
Quentin J
QJ
Fuller
Stephen D
SD
D000818:Animals; D020285:Cryoelectron Microscopy / Q000379:methods*; D006801:Humans; D021621:Imaging, Three-Dimensional; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure*; D046529:Microscopy, Electron, Transmission; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015302:Simian Immunodeficiency Virus / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure*; D014057:Tomography, X-Ray Computed; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure*
D008562:Membrane Glycoproteins; D014759:Viral Envelope Proteins; C069623:gp120 protein, Simian immunodeficiency virus