Cryo-Electron Microscopy Structure of Adenovirus Type 2 Temperature-Sensitive Mutant 1 Reveals Insight into the Cell Entry Defect

Journal of Virology - Tập 83 Số 15 - Trang 7375-7383 - 2009
Mariena Silvestry1, Steffen Lindert2,1, Jason G. Smith3, Oana Maier4, Christopher M. Wiethoff4, Glen R. Nemerow3, Phoebe L. Stewart1
1Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, 2215 Garland Avenue, Nashville, Tennessee 37232
2Department of Chemistry, Vanderbilt University, Nashville, Tennessee 37212
3Department of Immunology and Microbial Science, The Scripps Research Institute, 10550 North Torrey Pines Road, IMM-19, La Jolla, California 92037
4Department of Microbiology and Immunology, Loyola University Chicago Stritch School of Medicine, Loyola University Chicago, Building 105, 2160 South First Avenue, Maywood, Illinois 60153

Tóm tắt

ABSTRACT The structure of the adenovirus type 2 temperature-sensitive mutant 1 (Ad2 ts 1) was determined to a resolution of 10 Å by cryo-electron microscopy single-particle reconstruction. Ad2 ts 1 was prepared at a nonpermissive temperature and contains the precursor forms of the capsid proteins IIIa, VI, and VIII; the core proteins VII, X (mu), and terminal protein (TP); and the L1-52K protein. Cell entry studies have shown that although Ad2 ts 1 can bind the coxsackievirus and Ad receptor and undergo internalization via αv integrins, this mutant does not escape from the early endosome and is targeted for degradation. Comparison of the Ad2 ts 1 structure to that of mature Ad indicates that Ad2 ts 1 has a different core architecture. The Ad2 ts 1 core is closely associated with the icosahedral capsid, a connection which may be mediated by preproteins IIIa and VI. Density within hexon cavities is assigned to preprotein VI, and membrane disruption assays show that hexon shields the lytic activity of both the mature and precursor forms of protein VI. The internal surface of the penton base in Ad2 ts 1 appears to be anchored to the core by interactions with preprotein IIIa. Our structural analyses suggest that these connections to the core inhibit the release of the vertex proteins and lead to the cell entry defect of Ad2 ts 1.

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Journal of Virology

Tập 83 Số 15

7375-7383

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