The long-range goal is to understand the mechanism of assembly, entry, and uncoating of viruses, by examining their structures in detail and by testing proposed mechanisms in biochemical experiments and by site-directed mutagenesis. (1) We will determine the structure of SV40, a simple dsDNA tumor virus, by X- ray crystallography, to a resolution of at 3.5 angstroms, and we will construct a molecular model. We will also use electron microscopy or x-ray diffraction, as appropriate, to examine other forms of the virion -- empty capsids and disassembly intermediates in order to gain insight into uncoating mechanisms. (2) We will determine the structure of murine polyomavirus to the limit of recordable diffraction (presently about 6 angstroms, and using this map and the SV4O structure we will build an approximate molecular model. (3) We will use the models of both viruses to develop specific proposals concerning the role in assembly of S-S bonds, Ca++ ions and covalent modification. We will test proposals where possible by constructing site-directed mutants (in collaboration with Prof. T. Benjamin). (4) We will use difference maps to look directly for sialic-acid binding sites since poloma requires sialic acid for initial binding to cells. (5) We will determine the structure of single-shelled rotavirus SA-11 particles by X-ray crystallography. Crystals are at hand that diffract to at least 8 angstroms, and we will use these crystals to study binding of peptides from the RER """"""""receptor"""""""" of the single-shelled particles.
| Salgado, Eric N; Garcia Rodriguez, Brian; Narayanaswamy, Nagarjun et al. (2018) Visualization of Calcium Ion Loss from Rotavirus during Cell Entry. J Virol 92: |
| Chao, Luke H; Jang, Jaebong; Johnson, Adam et al. (2018) How small-molecule inhibitors of dengue-virus infection interfere with viral membrane fusion. Elife 7: |
| Salgado, Eric N; Upadhyayula, Srigokul; Harrison, Stephen C (2017) Single-particle detection of transcription following rotavirus entry. J Virol : |
| Harrison, Stephen C (2017) Protein tentacles. J Struct Biol 200:244-247 |
| Kim, Irene S; Jenni, Simon; Stanifer, Megan L et al. (2017) Mechanism of membrane fusion induced by vesicular stomatitis virus G protein. Proc Natl Acad Sci U S A 114:E28-E36 |
| Harrison, Stephen C (2015) Viral membrane fusion. Virology 479-480:498-507 |
| Mahmutovic, Selma; Clark, Lars; Levis, Silvana C et al. (2015) Molecular Basis for Antibody-Mediated Neutralization of New World Hemorrhagic Fever Mammarenaviruses. Cell Host Microbe 18:705-13 |
| Chao, Luke H; Klein, Daryl E; Schmidt, Aaron G et al. (2014) Sequential conformational rearrangements in flavivirus membrane fusion. Elife 3:e04389 |
| Abdelhakim, Aliaa H; Salgado, Eric N; Fu, Xiaofeng et al. (2014) Structural correlates of rotavirus cell entry. PLoS Pathog 10:e1004355 |
| Estrozi, Leandro F; Settembre, Ethan C; Goret, Gaël et al. (2013) Location of the dsRNA-dependent polymerase, VP1, in rotavirus particles. J Mol Biol 425:124-32 |
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