First publication of an atomic protein structure determined using the CEMF The collaborative effort of Dr. Youxing Jiang’s group (Physiology and Biophysics) and Dr. Xiao-chen Bai’s group (Biophysics and Cell biology) resulted in the world’s first 3D atomic structure of a mammalian ion channel Transient receptor potential mucolipin 1 (TRPML1) (Chen*, She* et al., Nature, 2017).
TRPML1 is an endo/lysosomal cation channel, and its loss-of-function mutations are the direct cause of Type IV mucolipidosis (MLIV), an autosomal recessive lysosomal storage disease. By using single particle cryo-electron microscopy (cryo-EM) in combination with mutagenesis, the TRPML1 structure reveals the PIP2 binding site and several key features in the selectivity filter that determine the cation ion selectivity. Through a particles sorting approach, the structure also reveals two equally distributed S4-S5 linker conformations in the closed channel, providing structural implication for the S4-S5 linker-mediated PIP2 gating mechanism among TRPML channels. This work marks the first publication of a structure determined using the university’s new $17 million Cryo-Electron Microscopy Facility (CEMF).