As a versatile tool in structural biology, single particle electron cryo-microscopy (cryo-EM) has achieved milestones of determining near atomic resolution three-dimensional (3D) reconstructions of non-enveloped viruses with icosahedral symmetry. Recent technological breakthroughs in single particle cryo-EM, particularly the development of novel dose-fractionated image acquisition method based on CMOS direct electron detection camera and robust algorithms for correction of motion induced image blurring, are transformative. It has enabled near atomic resolution structure determinations of a broad range of proteins complexes without the need of crystals.
Transient Receptor Potential (TRP) ion channels belong to a large and functionally diverse superfamily, second only to that of potassium channels. TRPV1 is the founding member of a subfamily of thermosensitive TRP channels.
Facilitated by novel single particle cryo-EM technology, we determined atomic structures of TRPV1 ion channels in three different conformations, ligand free apo state and in complexes with vanilloid agonist capsaicin, or resiniferatoxin and Double-Knot toxin. These atomic structures revealed structural architecture of TRPV1 ion channel, providing a structural blueprint for understanding unique aspects of TRP channel function. They also revealed gating mechanisms that differ from those of voltage gated ion channels.