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Biophysics and Biophysical Chemistry
725 N. Wolfe St
Baltimore, MD 21205
Receptor-ligand interactions and conformational transitions using computational and experimental approaches
Our lab is focused on understanding the molecular mechanisms of how multisubunit protein assemblies function. We are particularly interested in elucidating the structural thermodynamics that govern ligand binding, subunit assembly, and allosteric control of neuroreceptors such as ionotropic glutamate receptors (iGluRs). iGluRs are ligand-gated ion channels that mediate the majority of excitatory synaptic transmission in the central nervous system. iGluRs are important in synaptic plasticity, which underlies learning and memory, and these receptors have been implicated in a number of neurological disorders and diseases. Our approach relies on a combination of structural, biochemical, biophysical, and computational methods to define the architecture, function, and dynamics of macromolecular complexes. Molecular simulation, X-ray crystallography, small-angle X-ray scattering, and traditional biochemistry form the core of our approach.
Yu A, Alberstein R, Thomas A, Zimmet A, Grey R, Mayer ML, Lau AY. Molecular lock regulates binding of glycine to a primitive NMDA receptor. Proc. Natl. Acad. Sci. USA, 113, E6786–E6795, 2016.
Baranovic J, Chebli M, Salazar H, Carbone AL, Faelber K, Lau AY, Daumke O, Plested AJ. Dynamics of the Ligand Binding Domain Layer during AMPA Receptor Activation. Biophys. J., 110, 896–911, 2016.
Yao Y, Belcher J, Berger AJ, Mayer ML, Lau AY. Conformational analysis of NMDA receptor GluN1, GluN2, and GluN3 ligand-binding domains reveals subtype-specific characteristics. Structure, 21, 1788–1799, 2013.
Lau AY, Salazar H, Blachowicz L, Ghisi V, Plested AJ, Roux B. A conformational intermediate in glutamate receptor activation. Neuron, 79, 492–503, 2013.
Lau AY and Roux B. The hidden energetics of ligand binding and activation in a glutamate receptor. Nat. Struct. Mol. Biol., 18, 283–287, 2011.