[MOS] 4/19 - Modern Optics and Spectroscopy Virtual Seminar with Shwetha Srinivasan (MIT - Schlau-Cohen Group)

Christine Brooks cbrooks at mit.edu
Wed Apr 13 08:40:11 EDT 2022


There will be a virtual Modern Optics and Spectroscopy Seminar held next Tuesday, April 19 at 12pm. A short Q&A segment will immediately follow the conclusion of the seminar.

Zoom link: https://mit.zoom.us/j/99714325465?pwd=S2V6Q1p6UUkxTktPeEh1aU1XRUl0dz09
Password: 337483
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Shwetha Srinivasan
MIT – Schlau-Cohen Group

“Resolving conformational coupling across the membrane bilayer
of Epidermal Growth Factor Receptor with single-molecule spectroscopy”

Membrane receptors reside in complex environments along with their numerous extracellular binding partners or ligands to transduce information across the lipid bilayer. One such receptor protein is the epidermal growth factor receptor (EGFR) which plays a crucial role in cell signaling and is implicated in cancer. While the structures of the extracellular and intracellular regions of EGFR have been well elucidated individually, conformational coupling connecting these two regions during signal transduction is challenging to probe due to the mixture of hydrophobic and hydrophilic domains intrinsic to membrane proteins. We overcome these limitations by combining nanodiscs, which provide a near-native membrane environment to isolate full-length receptors, and single-molecule spectroscopy, which resolves the heterogeneous nature of these protein motions, to identify previously unknown coupling between the extracellular and intracellular domains of the epidermal growth factor receptor (EGFR). Furthermore, we untangle (1) the role of the complex membrane environment in the extracellular/intracellular conformational coupling of EGFR, uncovering the specific task of anionic lipids and cholesterol; and (2) the influence of the binding partners which determine EGFR’s downstream signaling and cellular process, ascertaining ligand-specific EGFR conformations. These results could be universal to other membrane receptors which share the same structural homology and perform other significant functions.


_____________________

Christine Brooks
Administrative Assistant
Massachusetts Institute of Technology
Department of Chemistry
77 Massachusetts Ave, 6-333
Cambridge, MA 02139
p: 617.253.7239
e: cbrooks at mit.edu<mailto:cbrooks at mit.edu>

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