The complex process of GETting tail-anchored membrane proteins to the ER

► Get3 is a central nucleotide hydrolase in the GET pathway, and models for interaction of tail-anchored (TA) proteins with Get3 include a binding groove formed by a Get3 dimer and a tetramer with a central hydrophobic chamber. ► ArsA is a representative member of a family of ATPases that includes Get3. ► Archaeal Get3 homologs are similar in structure and function to fungal Get3s suggesting a unique TA-targeting pathway in this domain. ► Some photosynthetic organisms have a conserved protein with structural similarity to Get3 that may be involved in biosynthesis of photosynthetic membranes. ► Get1 and Get2 form a membrane receptor for Get3/TA-protein complexes, and complexes of Get1 and Get2 soluble domains with [Get3] reveal a mechanism for release at the membrane.