Biophysical Society Thematic Meeting - November 16-20, 2015

Biophysics in the Understanding, Diagnosis, and Treatment of Infectious Diseases Poster Abstracts

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 Withdrawn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.

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