Leslie Salas Estrada

Research Interests

The focus of my research is to understand the molecular mechanisms by which different factors, such as membrane lipids, ligands and mutations, modulate the structure, dynamics and function of rhodopsin, the G protein-coupled receptor that mediates scotopic vision.

Lipids effects on rhodopsinRhodopsin is natively found in membranes that are enriched polyunsaturated fatty acids, such as DHA, which enhance its function.
Using microsecond-scale all-atom molecular dynamics simulations we have studied the effect of membrane lipids on rhodopsin along its photocycle. Our work suggest that phospholipids alter rhodopsin's structure and dynamics via both ligand-like and bulk-like effects.

Rhodopsin activation/deactivation
GPCR activation has remained elusive for standard simulation techniques due to its intrinsic timescales. We have implemented simple models (Go models) to try to bridge this gap. In these structure-based models, only native-like interactions are present, thus producing smoothed energy landscapes by construction where water and membrane interactions are implicitly accounted for. We are currently using this approach as a platform to study rhodopsin activation/deactivation, state interconversion in equilibrium and functionally relevant point-mutations.

Retinal analogs
In collaboration with the Feller lab, we are studying the effects of substitutions in rhodopsin's ligand (retinal) on the structure and dynamics of the receptor. In particular, we are interested on C9-methyl and C13-methyl substitutions, which have been shown to respectively decrease and increase the activity of the protein.

Publications
  1. Humberto Reyes-Pardo, Angel A. Barbosa-Camacho, Ana E. Pérez-Mejía, Bárbara Lara-Chacón, Leslie A. Salas-
    Estrada, Angélica Y. Robledo-Rivera, Gabriela M. Montero-Morán, Samuel Lara-González, Mónica R. Calera, and
    Roberto Sánchez-Olea. A nuclear export sequence in GPN-loop GTPase 1, an essential protein for nuclear targeting
    of RNA polymerase II, is necessary and sufficient for nuclear export.
    Biochim Biophys Acta, 1823(10): 1756–1766, 2012.

Contact

Email:
Letty_SalasEstrada[at]urmc.rochester.edu

Address:
Department of Biochemistry and Biophysics
University of Rochester, Medical Center, Box 712
Rochester, NY 14642

  Curriculum Vitae  |  ORCID   |   LinkedIn

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