Structures of the influenza virus HA2 fusion peptide in membrane deduced from our
NMR data.
We are a biophysical chemistry group that is focused on understanding the mechanism
of entry by viruses enveloped by a membrane. Many important human pathogens are enveloped
viruses, including Human Immunodeficiency (HIV), Influenza, Measles, Rabies, West
Nile, Zika, Ebola, SARS, and MERS. Each virus has evolved a protein in its membrane
that catalyzes the joining (“fusion”) of the virus membrane with the membrane of the
target cell. We are studying the glycoprotein 41 kDa (gp41) fusion protein of HIV
and hemagglutinin subunit 2 (HA2) fusion protein of influenza. Our work and contributions
include the protein structures and locations in membrane. We also study the changes
in membrane structure associated with the protein. A significant fraction of our effort
is in development and application of “solid-state”, i.e. anisotropic nuclear magnetic
resonance (NMR) to these proteins. We also apply a variety of other biophysical methods
including circular dichroism spectroscopy, fluorescence spectroscopy, hydrogen-deuterium
exchange mass spectrometry, X-ray crystallography, and electron microscopy. We also
have a significant effort in protein synthesis and chromatographic purification that
includes molecular biology and protein expression in bacteria, solid-phase peptide
synthesis, and native chemical ligation. A side-project in the laboratory is NMR analysis
of expressed proteins in bacterial inclusion bodies, which are commonly-formed solid
protein aggregates. We want to understand why these aggregates form, and the degree
of folding of individual proteins within the aggregates. Our NMR methodology focuses
on quantitative determination of distributions of populations of protein structures
and membrane locations, with a particular emphasis on the rotationalecho double-resonance
(REDOR) approach which is robust and amenable to quantitative analysis.
Models for influenza HA2-mediated membrane apposition based on our experimental data.
2H Nuclear Magnetic Resonance Spectroscopy Supports Larger Amplitude Fast Motion and
Interference with Lipid Chain Ordering for Membrane that Contains β Sheet Human Immunodeficiency Virus gp41 Fusion Peptide or Helical Hairpin Influenza
Virus Hemagglutinin Fusion Peptide at Fusogenic pH, U. Ghosh and D. P. Weliky, Biochim. Biophys. Acta 2020, 1862, 183404.
Hydrogen-Deuterium Exchange Supports Independent Membrane-Interfacial Fusion Peptide
and Transmembrane Domains in Subunit 2 of Influenza Virus Hemagglutinin Protein, a
Structured and Aqueous-Protected Connection between the Fusion Peptide and Soluble
Ectodomain, and the Importance of Membrane Apposition by the Trimer-of-Hairpins Structure, A. Ranaweera, P. U. Ratnayake, E. A. P. Ekanayaka, R. Declercq, and D. P. Weliky,
Biochemistry 2019, 58, 2432-2466.
The Stabilities of the Soluble Ectodomain and Fusion Peptide Hairpins of the Influenza
Virus Hemagglutinin Subunit II Protein Are Positively Correlated with Membrane Fusion, A. Ranaweera, P. U. Ratnayake, and D. P. Weliky, Biochemistry 2018, 57, 5480-5493.
Efficient Fusion at Neutral pH by Human Immunodeficiency Virus gp41 Trimers Containing
the Fusion Peptide and Transmembrane Domains, S. Liang, P. U. Ratnayake, C. Keinath, L. Jia, R. Wolfe, A. Ranaweera, and D. P. Weliky,
Biochemistry 2018, 57, 1219-1235.
Closed and Semiclosed Interhelical Structures in Membrane vs Closed and Open Structures
in Detergent for the Influenza Virus Hemagglutinin Fusion Peptide and Correlation
of Hydrophobic Surface Area with Fusion Catalysis, U. Ghosh, L. Xie, L. Jia, S. Liang, and D. P. Weliky, J. Am. Chem. Soc. 2015, 137, 7548-7551.
REDOR Solid-State NMR as a Probe of the Membrane Locations of Membrane- Associated
Peptides and Proteins, L. Jia, S. Liang, K. Sackett, L. Xie, U. Ghosh, and D. P. Weliky, J. Mag. Res. 2015, 253, 154-165.
CV
B.A., 1985, Swarthmore College
Ph.D., 1995, Univ. of Chicago
Postdoctoral Fellow, 1995-97, National Institutes of Health.
Awards
Year
Award
Organization
1998
New Faculty Award
Camille and Henry Dreyfus Foundation
1996
NIH Fellows Award for Research Excellence
National Institutes of Health
1995 - 1997
Postdoctoral Research Fellow
National Institutes of Health
1995
Ph.D.
The University of Chicago
1992
Research Fellow
AT&T Bell Laboratories
1991 - 1995
AT&T Ph.D. Scholar
AT&T
1988 - 1991
NSF Predoctoral Fellow
National Science Foundation
1987 - 1991
McCormick Fellow
1985
Member
Sigma Xi Honor Society (Swarthmore College)
1985
Phi Beta Kappa
Phi Beta Kappa (Swarthmore College)
1985
Bachelor of Arts with High Honors in Chemistry and Physics
