| 2234 Toward a High-Resolution 3D Structure of Human Cytomegalovirus | ||
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J.T. BECK1, Z.H. ZHOU1, T. XUE1, E. KE2, D. CHEN1, and F. LIU1, 1University of Texas at Houston-Medical School, USA, 2USA Human cytomegalovirus (HCMV) is a ubiquitous virus that can lead to severe morbidity or mortality in newborns and immunocompromised individuals. It can also cause various oral diseases ranging from oral ulcers to autoimmune diseases such as Sjögren's syndrome, which can lead to xerostomia. HCMV is the largest and most complex human virus, consisting of a core of dsDNA surrounded by an icosahedral capsid, a proteinaceous tegument layer, and a glycoprotein-containing outer envelope. The current drug regimen for HCMV is ineffective and suffers from drug resistance and recurrence of the disease. Objectives: Our research was aimed at determining a high-resolution three-dimensional (3D) structure of HCMV particles that could lead to the discovery of new targets of anti-HCMV drug design and more effective therapeutic intervention in the future. Methods: The major structural tool used was the newly emerging technique of electron cryomicroscopy, which allows the 3D reconstruction of macromolecular complexes without using crystals. The technique involves rapidly freezing specimens in liquid ethane, imaging them in an electron cryomicroscope, and recording a focal pair of images (one close-to-focus and one far-from-focus). The center and orientation parameters of the far-from-focus particle images were then determined with image processing via high performance computers. Results: We have determined and refined the orientation parameters of ~2300 far-from-focus HCMV particles, from which a 16-Å resolution 3D reconstruction was obtained. Conclusion: The improved resolution has allowed us to identify the symmetrical array of hexons, pentons, and connecting tegument proteins within the structure, which can be used as a blueprint of the structure of HCMV for future drug designs. Future studies to improve resolution will focus on refinement of the close-to-focus particles and merging them with the far-from-focus particles. This investigation was supported in part by NIH/NIDCR Training Grant T35DE07252-08. Jason.T.Beck@uth.tmc.edu | ||
| Seq #204 - Gram-positive Cocci: Molecular Biology II 11:00 AM-12:15 PM, Friday, 8 March 2002 San Diego Convention Center Exhibit Hall C | ||
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