Liao M, Cao E, Julius D, Cheng Y. Single particle electron cryo-microscopy of a mammalian ion channel. Curr Opin Struct Biol. 2014 Aug;27:1-7. doi: 10.1016/j.sbi.2014.02.005. Epub 2014 Mar 25. PMID: 24681231; PMCID: PMC4176607.

The transient receptor potential (TRP) ion channel family is large and functionally diverse, second only to potassium channels. Despite their prominence within the animal kingdom, TRP channels have resisted crystallization and structural determination for many years. This barrier was recently broken when the three-dimensional structure of the vanilloid receptor 1 (TRPV1) was determined by single particle electron cryo-microscopy (cryo-EM). Moreover, this is the first example in which the near atomic resolution structure of an integral membrane protein was elucidated by this technique and in a manner not requiring crystals, demonstrating the transformative power of single particle cryo-EM for revealing high-resolution structures of integral membrane proteins, particularly those of mammalian origin. Here we summarize technical advances, in both biochemistry and cryo-EM, that led to this major breakthrough.