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

• Published in: Current opinion in structural biology Vol. 22; no. 2; pp. 217 - 224
• Main Authors: Chartron, Justin W, Clemons, William M, Suloway, Christian JM
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.04.2012
• Subjects: Animals; Endoplasmic Reticulum - chemistry; Endoplasmic Reticulum - metabolism; Humans; Membrane Proteins - chemistry; Membrane Proteins - metabolism; Protein Binding; Protein Folding
• ISSN: 0959-440X; 1879-033X
• DOI: 10.1016/j.sbi.2012.03.001

► 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. Biosynthesis of membrane proteins requires that hydrophobic transmembrane (TM) regions be shielded from the cytoplasm while being directed to the correct membrane. Tail-anchored (TA) membrane proteins, characterized by a single C-terminal TM, pose an additional level of complexity because they must be post-translationally targeted. In eukaryotes, the GET pathway shuttles TA-proteins to the endoplasmic reticulum. The key proteins required in yeast (Sgt2 and Get1–5) have been under extensive structural and biochemical investigation during recent years. The central protein Get3 utilizes nucleotide linked conformational changes to facilitate substrate loading and targeting. Here we analyze this complex process from a structural perspective, as understood in yeast, and further postulate on similar pathways in other domains of life.