Structure of the sgt2 dimerization domain complexed with the get5 ubl domain involved in the targeting of tail-Anchored membrane proteins to the endoplasmic reticulum.
The insertion of tail-anchored membrane (TA) proteins into the appropriate
membrane is a post-translational event that requires stabilization of the
transmembrane domain and targeting to the proper destination. Sgt2, a small
glutamine-rich tetratricopeptide-repeat protein, is a heat-shock protein cognate
(HSC) co-chaperone that preferentially binds endoplasmic reticulum-destined TA
proteins and directs them to the GET pathway via Get4 and Get5. The N-terminal
domain of Sgt2 seems to exert dual functions. It mediates Get5 interaction and
allows substrate delivery to Get3. Following the N-terminus of Get5 is a
ubiquitin-like (Ubl) domain that interacts with the N-terminus of Sgt2. Here,
the crystal structure of the Sgt2 dimerization domain complexed with the Get5
Ubl domain (Sgt2N-Get5Ubl) is reported. This complex reveals an intimate
interaction between one Sgt2 dimer and one Get5 monomer. This research further
demonstrates that hydrophobic residues from both Sgt2 and Get5 play an important
role in cell survival under heat stress. This study provides detailed molecular
insights into the specific binding of this GET-pathway complex.
