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.Membrane fusion is an essential process for a variety of cellular events. In particular, it is the basic mode of entry by enveloped viruses into cells. Viral fusion proteins contain segments of 10-30 residues, called fusion peptides (FP), which insert into the host cell membrane. Their insertion is followed by formation of a fusion pore and by merging of the viral membrane into the host membrane. Here we propose to investigate the effects of FP on the behavior of lipid membrane dispersions able to transform from lamellar into inverted bicontinuous cubic phase. The latter transformation actually occurs as a result of multiple, cooperative fusion events and thus represents an appropriate model of fusion pore formation (Fig. 1). Time-resolved X-ray diffraction is the method of choice for studies on the pathway and kinetics of this transition. We have collected X-ray diffraction evidence a documenting the ability of major membrane lipid classes to transform from lamellar into well-ordered bilayer cubic phases. In preliminary work, we found that FP strongly favor and accelerate cubic phase formation. These findings make it possible to focus on their structural roles in the present project. Using sets of synthetic, well defined wild-type and mutant, non-functional peptide sequences, our major goal is to characterize in a novel, quantitative way the FP effects on the membrane structure and stability. We also plan to investigate the observed lipid specificity of some FPs and to elucidate and quantify the fusion competence of the major biomembrane lipid classes.
| 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 |
| 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 |
| 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 |
| 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 |
Showing the most recent 10 out of 100 publications
