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    Rudolf-Virchow-Zentrum - Center for Integrative and Translational Bioimaging

    RVZ Gastvortrag: Prof. Hugo Sanabria

    "Dynamic Organization in the Supertertiary Structure of PSD-95 Scaffold Protein"
    Datum: 19.11.2020, 17:00 - 18:00 Uhr
    Vortragende*r: Prof. Dr. Hugo Sanabria
    Source:https://www.clemson.edu/

    Prof. Dr. Hugo Sanabria von der Clemson University (South Carolina, USA) wird am 19.11.20 einen
    Zoom-Vortrag zum Thema "Dynamic Organization in the Supertertiary Structure of PSD-95 Scaffold Protein" halten.

    Der Zoom-Link wird noch bekannt gegeben.

    "PSD-95, a member of the membrane-associated guanylate kinase (MAGUK) family, is a scaffold protein responsible for clustering ionotropic glutamate receptors and ion channels at the postsynaptic membrane of the excitatory synapse. The interdomain organization within the supertertiary structure of PSD-95 reveals two independent supramodules, the PDZ1-PDZ2 tandem and the PDZ3-SH3-GuK core. A similar supramodule organization is present within members of the synaptic MAGUK family. Therefore, uncovering the intra- and inter-module structural dynamics is crucial for elucidating the functional role of PSD-95 and other similar scaffolding proteins. Here, we present a hybrid/integrative study revealing the supertertiary structural dynamics of PSD-95 by combining replica-exchange discrete molecular dynamics simulations (rxDMD), single-molecule FRET (smFRET) experiments in Multiparameter Fluorescence Detection mode, and disulfide mapping gel assays. We find that in silico accessible volume simulations using the structures from the rxDMD trajectories help us identify structural clusters consistent with our experimentally determined inter-dye distances. Also, we use disulfide mapping to validate and refine structural models for the two supramodules. Our results highlight the hybrid/integrative approach's predictive power in deciphering the dynamic organization of the supertertiary structure of PSD-95."

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