(A) EGFR exists in a tethered monomer or an inactive dimer formation. Upon EGF binding, it adopts an extended dimer conformation and undergoes auto-transphosphorylation. Phosphorylated dimers recruit adaptor proteins to EGFR, resulting in activation of the Ras-MAPK pathway.

(B) EGF binding to EGFR also results in rapid changes in spatial organization from monomers (i) to dimers (ii); to higher order multimers and nanoscale clusters (iii-iv); to micron scale clusters in clathrin-coated pits (v); and, finally, to endosomes (vi).

(C) A chemical genetic system utilizing a SNAP-tag on the N terminus of full-length EGFR and BG-modified DNA dimers as crosslinkers.