The natural history of Get3-like chaperones

TY - JOUR

T1 - The natural history of Get3-like chaperones

AU - Farkas, Ákos

AU - De Laurentiis, Evelina Ines

AU - Schwappach, Blanche

N1 - © 2019 The Authors. Traffic published by John Wiley & Sons Ltd.

PY - 2019/5

Y1 - 2019/5

N2 - Get3 in yeast or TRC40 in mammals is an ATPase that, in eukaryotes, is a central element of the GET or TRC pathway involved in the targeting of tail-anchored proteins. Get3 has also been shown to possess chaperone holdase activity. A bioinformatic assessment was performed across all domains of life on functionally important regions of Get3 including the TRC40-insert and the hydrophobic groove essential for tail-anchored protein binding. We find that such a hydrophobic groove is much more common in bacterial Get3 homologs than previously appreciated based on a directed comparison of bacterial ArsA and yeast Get3. Furthermore, our analysis shows that the region containing the TRC40-insert varies in length and methionine content to an unexpected extent within eukaryotes and also between different phylogenetic groups. In fact, since the TRC40-insert is present in all domains of life, we suggest that its presence does not automatically predict a tail-anchored protein targeting function. This opens up a new perspective on the function of organellar Get3 homologs in plants which feature the TRC40-insert but have not been demonstrated to function in tail-anchored protein targeting. Our analysis also highlights a large diversity of the ways Get3 homologs dimerize. Thus, based on the structural features of Get3 homologs, these proteins may have an unexplored functional diversity in all domains of life.

AB - Get3 in yeast or TRC40 in mammals is an ATPase that, in eukaryotes, is a central element of the GET or TRC pathway involved in the targeting of tail-anchored proteins. Get3 has also been shown to possess chaperone holdase activity. A bioinformatic assessment was performed across all domains of life on functionally important regions of Get3 including the TRC40-insert and the hydrophobic groove essential for tail-anchored protein binding. We find that such a hydrophobic groove is much more common in bacterial Get3 homologs than previously appreciated based on a directed comparison of bacterial ArsA and yeast Get3. Furthermore, our analysis shows that the region containing the TRC40-insert varies in length and methionine content to an unexpected extent within eukaryotes and also between different phylogenetic groups. In fact, since the TRC40-insert is present in all domains of life, we suggest that its presence does not automatically predict a tail-anchored protein targeting function. This opens up a new perspective on the function of organellar Get3 homologs in plants which feature the TRC40-insert but have not been demonstrated to function in tail-anchored protein targeting. Our analysis also highlights a large diversity of the ways Get3 homologs dimerize. Thus, based on the structural features of Get3 homologs, these proteins may have an unexplored functional diversity in all domains of life.

KW - Adenosine Triphosphatases/chemistry

KW - Animals

KW - Arsenite Transporting ATPases/chemistry

KW - Escherichia coli Proteins/chemistry

KW - Evolution, Molecular

KW - Guanine Nucleotide Exchange Factors/chemistry

KW - Humans

KW - Ion Pumps/chemistry

KW - Molecular Chaperones/chemistry

KW - Multienzyme Complexes/chemistry

KW - Saccharomyces cerevisiae Proteins/chemistry

KW - Sequence Homology, Amino Acid

U2 - 10.1111/tra.12643

DO - 10.1111/tra.12643

M3 - SCORING: Review article

C2 - 30972921

VL - 20

SP - 311

EP - 324

JO - TRAFFIC

JF - TRAFFIC

SN - 1398-9219

IS - 5

ER -