Mapping the structure and function of the E1 and E2 glycoproteins in alphaviruses.
The 9 A resolution cryo-electron microscopy map of Sindbis virus presented here provides structural information on the polypeptide topology of the E2 protein, on the interactions between the E1 and E2 glycoproteins in the formation of a heterodimer, on the difference in conformation of the two types of trimeric spikes, on the interaction between the transmembrane helices of the E1 and E2 proteins, and on the conformational changes that occur when fusing with a host cell. The positions of various markers on the E2 protein established the approximate topology of the E2 structure. The largest conformational differences between the icosahedral surface spikes at icosahedral 3-fold and quasi-3-fold positions are associated with the monomers closest to the 5-fold axes. The long E2 monomers, containing the cell receptor recognition motif at their extremities, are shown to rotate by about 180 degrees and to move away from the center of the spikes during fusion.
Mukhopadhyay
Suchetana
S
Department of Biological Sciences, Purdue University, West Lafayette, Indiana 47907, USA. sumukhop@indiana.edu
Zhang
Wei
W
Gabler
Stefan
S
Chipman
Paul R
PR
Strauss
Ellen G
EG
Strauss
James H
JH
Baker
Timothy S
TS
Kuhn
Richard J
RJ
Rossmann
Michael G
MG
D020285:Cryoelectron Microscopy; D018360:Crystallography, X-Ray; D008562:Membrane Glycoproteins / Q000737:chemistry* / Q000502:physiology* / Q000648:ultrastructure; D019590:Nucleocapsid Proteins / Q000737:chemistry / Q000502:physiology / Q000648:ultrastructure; D025941:Protein Interaction Mapping; D017434:Protein Structure, Tertiary; D012845:Sindbis Virus / Q000737:chemistry* / Q000502:physiology* / Q000648:ultrastructure; D014759:Viral Envelope Proteins / Q000737:chemistry* / Q000502:physiology* / Q000648:ultrastructure; D014760:Viral Fusion Proteins / Q000737:chemistry / Q000502:physiology / Q000648:ultrastructure
D008562:Membrane Glycoproteins; D019590:Nucleocapsid Proteins; D014759:Viral Envelope Proteins; D014760:Viral Fusion Proteins; C022012:glycoprotein E1, Sindbis virus; C064950:glycoprotein E2, Sindbis virus