STRUCTURAL STUDIES ON ADENOVIRUS CAPSIDS AND ASSOCIATED STRUCTURAL PROTEINS

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Adenoviruses (Ad) are non-enveloped DNA viruses with icosahedral symmetry and a diameter of approximately 950A. Their association with acute respiratory, gastrointestinal and ocular infections as well as use in gene delivery applications has drawn intense interest from basic and medical researchers. Approximately 28% of all viral vector gene therapy trials in the U.S. currently employ adenovirus, primarily for the treatment of cardiovascular diseases and cancer. It has been difficult to crystallize the entire adenovirus due to long protruding fibers from the vertices. We recently crystallized a form of chimeric adenovirus that diffracts beyond 5A resolution. We have collected partial dataset to 8A resolution at the BIOCARS and GMCA beam lines at APS on capillary mounted crystals. Recently we have successfully identified a cryo condition where the adenovirus crystals can be frozen. We would like to collect a complete data set from cryo frozen crystals as well as from capillary mounted crystals. Knowledge of the entire structure of adenovirus provides the information on the three dimensional fold and interactions between various proteins as well as various antigenic regions of the virus. Furthermore, the enormity of this molecule of the size of 150Mda and ~1000A in diameter make it a largest structure solved by the x-ray crystallography. Knowledge gained in solving this mega structure advances the technologies required for solving similar kinds of large structures.