Deciphering the molecular organization of GET pathway chaperones through native mass spectrometry.

ABSTRACT: Get3/4/5 chaperone complex is responsible for targeting C-terminal tail-anchored membrane proteins to the endoplasmic reticulum. Despite the availability of several crystal structures of independent proteins and partial structures of subcomplexes, different models of oligomeric states and structural organization have been proposed for the protein complexes involved. Here, using native mass spectrometry (Native-MS), coupled with intact dissociation, we show that Get4/5 exclusively forms a tetramer using both Get5/5 and a novel Get4/4 dimerization interface. Addition of Get3 to this leads to a hexameric (Get3)₂-(Get4)₂-(Get5)₂ complex with closed-ring cyclic architecture. We further validate our claims through molecular modeling and mutational abrogation of t

SUBMITTER: Giska F 

PROVIDER: S-EPMC9034188 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature