Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California, USA.
Division of Biochemical Sciences, CSIR-National Chemical Laboratory, Pune, India.
J Biol Chem. 2023 Jun;299(6):104752. doi: 10.1016/j.jbc.2023.104752. Epub 2023 Apr 24.
Homologs of the protein Get3 have been identified in all domains yet remain to be fully characterized. In the eukaryotic cytoplasm, Get3 delivers tail-anchored (TA) integral membrane proteins, defined by a single transmembrane helix at their C terminus, to the endoplasmic reticulum. While most eukaryotes have a single Get3 gene, plants are notable for having multiple Get3 paralogs. Get3d is conserved across land plants and photosynthetic bacteria and includes a distinctive C-terminal α-crystallin domain. After tracing the evolutionary origin of Get3d, we solve the Arabidopsis thaliana Get3d crystal structure, identify its localization to the chloroplast, and provide evidence for a role in TA protein binding. The structure is identical to that of a cyanobacterial Get3 homolog, which is further refined here. Distinct features of Get3d include an incomplete active site, a "closed" conformation in the apo-state, and a hydrophobic chamber. Both homologs have ATPase activity and are capable of binding TA proteins, supporting a potential role in TA protein targeting. Get3d is first found with the development of photosynthesis and conserved across 1.2 billion years into the chloroplasts of higher plants across the evolution of photosynthesis suggesting a role in the homeostasis of photosynthetic machinery.
Get3 蛋白的同源物已在所有领域被鉴定出来，但仍有待全面描述。在真核细胞质中，Get3 将尾部锚定（TA）的整合膜蛋白递送到内质网，这些蛋白的 C 末端有一个单一的跨膜螺旋。虽然大多数真核生物只有一个 Get3 基因，但植物的特点是有多个 Get3 基因的同源物。Get3d 在陆生植物和光合细菌中是保守的，包括一个独特的 C 末端 α-晶状体结构域。在追踪 Get3d 的进化起源后，我们解析了拟南芥 Get3d 的晶体结构，确定了它在叶绿体中的定位，并提供了 TA 蛋白结合的证据。该结构与一种蓝细菌 Get3 同源物相同，在这里进一步进行了细化。Get3d 的独特特征包括不完整的活性位点、apo 状态下的“封闭”构象和疏水性腔。这两种同源物都具有 ATP 酶活性，并且能够结合 TA 蛋白，支持其在 TA 蛋白靶向中的潜在作用。Get3d 是随着光合作用的发展而首次发现的，并在光合作用进化的 12 亿年中保守存在于高等植物的叶绿体中，这表明它在光合作用机器的动态平衡中发挥了作用。
