Structures of Get3, Get4, and Get5 provide new models for TA membrane protein targeting.
The GET pathway, using several proteins (Gets 1-5 and probably Sgt2), posttranslationally conducts tail-anchored (TA) proteins to the endoplasmic reticulum (ER). At the ER, TA proteins are inserted into the lipid bilayer and then sorted and directed to their respective destinations in the secretory pathway. Until last year, there was no structural information on any of the GET components but now there are ten crystal structures of Get3 in a variety of nucleotide-bound states and conformations. The structures of Get4 and a portion of Get5 also emerged in 2010. This minireview provides a detailed comparison of the GET structures and discusses their mechanistic relevance to TA protein insertion. It also addresses the outstanding gaps in detailed molecular information on this system, including the structures of Get5, Sgt2, and the transmembrane complex comprising Get1 and Get2.
Simpson
Peter J
PJ
Division of Molecular Biosciences, Imperial College London, Exhibition Road, South Kensington, London SW7 2AZ, UK.
Schwappach
Blanche
B
Dohlman
Henrik G
HG
Isaacson
Rivka L
RL
D000251:Adenosine Triphosphatases / Q000737:chemistry* / Q000378:metabolism; D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D020662:Guanine Nucleotide Exchange Factors / Q000737:chemistry* / Q000378:metabolism; D008565:Membrane Proteins; D008954:Models, Biological; D008958:Models, Molecular; D021381:Protein Transport; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D025801:Ubiquitin / Q000737:chemistry* / Q000378:metabolism
D002352:Carrier Proteins; C548889:GET4 protein, S cerevisiae; D020662:Guanine Nucleotide Exchange Factors; C510068:Mdy2 protein, S cerevisiae; D008565:Membrane Proteins; D029701:Saccharomyces cerevisiae Proteins; D025801:Ubiquitin; D000251:Adenosine Triphosphatases; C529048:Get3 protein, S cerevisiae