Abstract by Joseph Bohman
Chemistry and Biochemistry
Structural Determination of the CCT:PhLP1:Gβ5 folding complex
Before the Gβ subunit of the G-protein heterotrimer can be assembled, it must first be folded by the cytosolic chaperonin CCT and by the co-chaperone Phosducin-like Protein 1 (PhLP1). PhLP1 has been observed to increase the affinity of the Gβ5 for CCT. Here we present a structure of CCT in complex with PhLP1 and Gβ5 at less than 4 angstrom resolution. Using a combination of cryo-electron microscopy and crosslinking coupled with mass spectrometry, we found this structure differs from previously published complexs of CCT with PhLP1. In the case of Gβ5, the substrate sits deep in the CCT folding chamber between the CCT rings. The position of PhLP1 is also distinct, presumably to accommodate the differences in substrate position. These structural observations provide insight into the different roles PhLP1 plays in folding Gβ5 and its subsequent dimerization with other proteins.