Biophysical Society Thematic Meeting| Aussois 2019

Biology and Physics Confront Cell-Cell Adhesion

Thursday Speaker Abstracts

PHOSPHOTYROSINE-DRIVING PROTEIN CONDENSATION PHASE TRANSITIONS AND THE MECHANICS OF SIGNALING THROUGH THE T CELL RECEPTOR Jay T. Groves ; 1 UC Berkeley, Chemistry, Berkeley, California, USA Activation of the T cell receptor (TCR) leads to phosphorylation of the intrinsically disordered scaffold protein, LAT, on the membrane. Grb2 is recruited to phosphorylated tyrosine (pY) sites on LAT, which subsequently recruits the Ras activator, SOS. SOS is bivalent for Grb2 and this whole system can undergo a gelation phase transition into a condensed 2D phase of associated proteins on the membrane surface. This presentation will discuss a variety of new experiments mapping the early mechanics of TCR signaling and the role of the LAT condensation phase transition as a signal regulatory mechanism. One fundamental finding is that a kinetic proof reading mechanism, based on the molecular binding dwell time of SOS at the membrane, may provide a critical level of noise suppression in TCR signaling, enabling the T cell to be a single molecule sensor, even in noisy environments. Other aspects of the phase transition in T cell signal regulation will also be discussed.

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