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Biophysics in the Understanding, Diagnosis, and Treatment of Infectious Diseases Poster Abstracts
77
43-POS
Board 43
Ozlem Tastan Bishop
.
Rhodes University, Grahamstown, South Africa.
Withdrawn
44-POS
Board 44
Entropy-Driven Biological Processes: Signaling Mechanisms in Controlled Entry of
Enveloped Viruses into Host Cells
Sameer Varma
, Priyanka Dutta, Mohsen Botlani, Nalvi Duro.
University of South Florida, Tampa, USA.
The activities of many proteins, including GPCRs, T-cell receptors and nuclear transcription
factors, are controlled by shifts in their conformational densities, and not just through changes in
their minimum-energy structures. A primary challenge faced in the study of such proteins and
their response functions to biological stimuli concerns the characterization of their thermal
motions. Here we will present the development of new generalized methods to evaluate
differences between conformational ensembles (JCTC 2013, 9:868; Proteins 2014, 82:3241). In
addition, we will present how we are using these methods in conjunction with accelerated
conformational sampling techniques and wet-lab experiments to illuminate the molecular details
underlying the regulated entry of enveloped paramyxoviruses into host cells. Paramyxoviruses,
such as the Measles, and the emerging, highly-lethal Nipah, regulate their entry into host cells
via a combination of two separate protein-protein interactions. The signal for their entry
originates at the interface formed between one of their membrane proteins and those of the host
cell. This protein-protein interface sandwiches a substantially large amount of water, which we
find is vital to the inception of the signal (JPCB 2014, 118:14795). The signal then transduces
from the receptor binding domain of this viral protein to another domain, traversing a distance >
2 nm, where it activates a second viral membrane protein that facilitates virus-host membrane
fusion. A large part of this intricate allosteric signal is entropic in nature, as also evident from
crystallographic studies that reveal minor host-induced changes in viral protein structure (RMSD
< 0.2 nm). Our investigations are providing the first atomic-level insights into these signaling
processes, and we anticipate that our methods will also benefit the study of other entropically-
driven biomolecular machines.