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J Virol, February 1998, p. 1534-1541, Vol. 72, No. 2
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Structural Localization of the E3 Glycoprotein in Attenuated Sindbis Virus Mutants

A. M. Paredes,1,* H. Heidner,2 P. Thuman-Commike,3 B. V. Venkataram Prasad,1 R. E. Johnston,2 and W. Chiu1

National Center for Macromolecular Imaging, Verna and Marrs McLean Department of Biochemistry, Baylor College of Medicine, Houston, Texas 770301; Department of Microbiology and Immunology, School of Medicine, University of North Carolina, Chapel Hill, North Carolina 275992; and Department of Computational and Applied Mathematics, The W. M. Keck Center for Computational Biology, Rice University, Houston, Texas 77005-18923

Received 23 June 1997/Accepted 16 October 1997

We have determined the three-dimensional structures of the wild-type Sindbis virus and two of its mutants that retain the E3 sequence within PE2. Using difference imaging between these mutants and the wild-type virus, we have assigned a location for the 64-amino-acid sequence corresponding to E3 in the mutant spike complex. In the wild-type virus, the spike is composed of an E1-E2 heterotrimer. The E3 protein was found to protrude midway between the center of the spike complex and the tips. Based on these results and the work of others, we propose a distribution for the functional domains of the spike proteins within the structure of wild-type Sindbis virus. Within the structure of the virus, the E1 domains form the central portion of the spike complex, while the tips are formed by the E2 domains that flare out from the center of the complex. The structural similarity between these Sindbis virus mutants and Ross River virus suggests that E3 may also be present in the latter, which is also a member of the Alphavirus genus.

* Corresponding author. Mailing address: National Center for Macromolecular Imaging, Verna and Marrs McLean Department of Biochemistry, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030. Phone: (713) 798-6989. Fax: (713) 796-9438. E-mail: angel{at}tiger.3dem.bioch.bcm.tmc.edu.




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