3.A.19.1.4
ArsA1 of 777 aas.  ATPase is required for the post-translational delivery of tail-anchored (TA) proteins to the chloroplast. It is also required for the accumulation of TOC34, an essential component of the outer chloroplast membrane translocon (TOC) complex (Formighieri et al. 2013, Maestre-Reyna et al. 2017). ArsA1 recognizes and selectively binds the transmembrane domain of TA proteins in the cytosol. This complex then targets the protein to the chloroplast, where the tail-anchored protein is released for insertion. This process is regulated by ATP binding and hydrolysis (Maestre-Reyna et al. 2017). Both ArsA proteins exhibit oxyanion-independent ATPase activity, but co-expression of ArsA proteins with TA-transmembrane regions showed not only that the former interacts with the latter, but that ArsA1 does not share the same ligand specificity as ArsA2. ArsA1 mainly carries TA-proteins to the chloroplast, while ArsA2 carries them to the endoplasmic reticulum (Maestre-Reyna et al. 2017). Lin et al. 2019 presented crystal structures of algal ArsA1 (a Get3 homolog) in a distinct nucleotide-free open state and bound to adenylyl-imidodiphosphate. This approximately 80-kDa protein possesses a monomeric architecture, with two ATPase domains in a single polypeptide chain. It is capable of binding chloroplast (TOC34 and TOC159) and mitochondrial (TOM7) TA proteins based on features of its transmembrane domain as well as the regions immediately before and after the transmembrane domain. Several helices located above the TA-binding groove comprise the interlocking hook-like motif implicated by mutational analyses in TA substrate recognition. The data of Lin et al. 2019 provide insights into the molecular basis of the highly specific selectivity of interactions of algal ArsA1 with the correct sets of TA substrates before membrane targeting in plant cells.