This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.It is now believed that any successful AIDS vaccine will need to include an Env-based immunogen to elicit effective humoral immunity. Structural information is important for rational design of Env-based immunogens, but because an adequate picture of the intact envelope protein is still missing, most proposals for 'designed' immunogens involve a substantial amount of guesswork. The envelope glycoprotein (Env) of HIV/SIV mediates viral attachment and membrane fusion. Fusion is carried out by large-scale structural rearrangements, induced by binding of Env to receptor (CD4) and co-receptor (CCR5 or CXCR4). Env, synthesized as a precursor polypeptide, gp160, is present on mature virions as a trimeric assembly of a cleaved product, gp120/gp41. Structures have been determined of the gp120 fragment, both before and after CD4 binding, and of the gp41 ectodomain after the fusion-inducing conformational change. The challenges of crystallizing the heavily glycosylated full trimer have yet to be overcome, however, even after many years of effort on the part of numerous groups. Nonetheless, carefully performed SAXS experiments can allow us to assemble the partial structures already determined into a sensible picture for the intact protein. Preliminary experiments at 18-ID, taking advantage of the inline FPLC, indicate that this type of structural study is feasible. Because we have now succeeded in expressing and purifying a series of stable forms of gp140, from SIV and HIV isolates, we believe that suitable SAXS experiments can lead to models that will integrate the known gp120 structures into a more useful picture of the intact viral antigen.
| Orgel, Joseph P R O; Sella, Ido; Madhurapantula, Rama S et al. (2017) Molecular and ultrastructural studies of a fibrillar collagen from octocoral (Cnidaria). J Exp Biol 220:3327-3335 |
| Yazdi, Aliakbar Khalili; Vezina, Grant C; Shilton, Brian H (2017) An alternate mode of oligomerization for E. coli SecA. Sci Rep 7:11747 |
| Sullivan, Brendan; Robison, Gregory; Pushkar, Yulia et al. (2017) Copper accumulation in rodent brain astrocytes: A species difference. J Trace Elem Med Biol 39:6-13 |
| Morris, Martha Clare (2016) Nutrition and risk of dementia: overview and methodological issues. Ann N Y Acad Sci 1367:31-7 |
| Robison, Gregory; Sullivan, Brendan; Cannon, Jason R et al. (2015) Identification of dopaminergic neurons of the substantia nigra pars compacta as a target of manganese accumulation. Metallomics 7:748-55 |
| Gelfand, Paul; Smith, Randy J; Stavitski, Eli et al. (2015) Characterization of Protein Structural Changes in Living Cells Using Time-Lapsed FTIR Imaging. Anal Chem 87:6025-31 |
| Liang, Wenguang G; Ren, Min; Zhao, Fan et al. (2015) Structures of human CCL18, CCL3, and CCL4 reveal molecular determinants for quaternary structures and sensitivity to insulin-degrading enzyme. J Mol Biol 427:1345-1358 |
| Zhou, Hao; Li, Shangyang; Badger, John et al. (2015) Modulation of HIV protease flexibility by the T80N mutation. Proteins 83:1929-39 |
| Nobrega, R Paul; Arora, Karunesh; Kathuria, Sagar V et al. (2014) Modulation of frustration in folding by sequence permutation. Proc Natl Acad Sci U S A 111:10562-7 |
| Jiao, Lianying; Ouyang, Songying; Shaw, Neil et al. (2014) Mechanism of the Rpn13-induced activation of Uch37. Protein Cell 5:616-30 |
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