Avid Bioservices Inc (CDMO)

[biopharm]

Interaction of the Dengue Virus Fusion Peptide with Membranes Assessed by NMR: The Essential Role of the Envelope Protein Trp101 for Membrane Fusion

ABSTRACT
Dengue virus (DV) infection depends on a step of membrane fusion, which occurs in the acidic environment of the endosome. This process is mediated by virus surface envelope glycoprotein, in which the loop between residues D98-G112 is considered to be crucial, acting as a fusion peptide. Here, we have characterized functionally and structurally the interaction between the DV fusion peptide and different model membranes by fluorescence and NMR. Its interaction was strongest in dodecylphosphocholine (DPC) micelles and anionic phosphatidylcholine/phosphatidylglycerol vesicles, the only vesicle that was fused by DV fusion peptide. The three-dimensional structure of DV fusion peptide bound to DPC micelles was solved by solution homonuclear NMR with an r.m.s.d. of 0.98 A. The most striking result obtained from the solution structure was the hydrophobic triad formed by residues W101, L107, and F108, pointing toward the same direction, keeping the segment between G102 and G106 in a loop conformation. The interaction of DV fusion peptide with phosphatidylcholine/phosphatidylglycerol vesicles was also mapped by transfer-nuclear Overhauser enhancement (NOE) experiments, in which the majority of the NOE cross-peaks were from the hydrophobic triad, corroborating the DPC-bound structure. Substitution of the residue W101 by an alanine residue completely abolished membrane binding and, thus, fusion by the peptide and its NOE cross-peaks. In conclusion, the 15-residue DV fusion peptide has intrinsic ability to promote membrane fusion, most likely due to the hydrophobic interaction among the residues W101, L107, and F108, which maintains its loop in the correct spatial conformation.

Interaction of the Dengue Virus Fusion Peptide with Membranes Assessed by NMR: The Essential Role of the Envelope Protein Trp101 for Membrane Fusion - ResearchGate.

http://www.researchgate.net/publication/26683286_Interaction_of_the_Dengue_Virus_Fusion_Peptide_with_Membranes_Assessed_by_NMR_The_Essential_Role_of_the_Envelope_Protein_Trp101_for_Membrane_Fusion

-----------------------------------------------------

So NMR can be utilized to really see what is going on and helps with all interactions re: PS Targeting

----------------------------------------------------

Brookhaven Women in Science Talk at Brookhaven Lab on Friday, 10/16: 'Microscopes and Biomolecules in the Toy Box'

October 7, 2015

UPTON, NY — Ana-Carolina Zeri of Brazilian Biosciences National Laboratory will give a talk, "Microscopes and Biomolecules in the Toy Box," at the U.S. Department of Energy's Brookhaven National Laboratory on Friday, October 16, at 4:30 p.m. in the Physics Department seminar room. Sponsored by Brookhaven Science Associates and Brookhaven Women in Science, the talk is free and open to the public. All visitors to the Laboratory 16 and older must bring a photo I.D.

The Brazilian Biosciences National Laboratory, LNBio, is part of a complex of national laboratories, Centro Nacional de Pesquisa em Energy e Materiais (CNPEM) in Brazil. The complex includes the site of the first Synchrotron Light Source built in the Southern Hemisphere, the "Laboratorio Nacional de Luz Sincrotron," and future site of the next generation source, Sirius the CPEM, and is also home to Laboratorio Nacional de Ciencia e Tecnologia do Bioetanol (CTBE) and the Laboratorrio Nacional de Nanotechnologia (LNNano).

For her talk at Brookhaven, Zeri will discuss her activities as a scientist and an educator, and how her team uses nuclear magnetic resonance spectroscopy (NMR), to study biological samples with applications in cancer research, bacterial growth machinery, and pathogen defense mechanisms. The NMR techniques enable scientists to determine the shape (at an atomic level) of molecules, such as proteins, and investigate minute differences in the composition of biofluids, such as saliva, blood plasma and urine.

Winner of an Eisenhower Fellowship to enhance science, technology, engineering, and math (STEM) educational programs, Zeri will also discuss her personal experiences and challenges as a woman in the world of science. She will also present how she has combined her research with her passion for education and the social advancement of young women. She is also interested in the portrayal of girls and women in the media and how this impacts their career aspirations.

Ana Zeri completed her Ph.D in the United States and returned to Brazil where she currently is a principal investigator at Brazilian Biosciences National Laboratory. In addition to her research using nuclear magnetic resonance spectroscopy, Zeri also volunteers as a leader in educational outreach programs. Her future plans include studying the importance of science education in public policy.

https://www.bnl.gov/newsroom/news.php?a=11779

Still nice to see that Alison Stopeck goes to Stony Brook and they work closely with Brookhaven.