mitochondrial unfolded protein response / protein import into mitochondrial intermembrane space / GroEL-GroES complex / apoptotic mitochondrial changes / positive regulation of interferon-alpha production / chaperone cofactor-dependent protein refolding / ATP-dependent protein folding chaperone / positive regulation of interleukin-6 production / positive regulation of type II interferon production / positive regulation of T cell activation ...mitochondrial unfolded protein response / protein import into mitochondrial intermembrane space / GroEL-GroES complex / apoptotic mitochondrial changes / positive regulation of interferon-alpha production / chaperone cofactor-dependent protein refolding / ATP-dependent protein folding chaperone / positive regulation of interleukin-6 production / positive regulation of type II interferon production / positive regulation of T cell activation / unfolded protein binding / protein-folding chaperone binding / protein refolding / response to heat / ATP binding / identical protein binding / metal ion binding 類似検索 - 分子機能
ジャーナル: PLoS One / 年: 2020 タイトル: Structure and conformational cycle of a bacteriophage-encoded chaperonin. 著者: Andreas Bracher / Simanta S Paul / Huping Wang / Nadine Wischnewski / F Ulrich Hartl / Manajit Hayer-Hartl / 要旨: Chaperonins are ubiquitous molecular chaperones found in all domains of life. They form ring-shaped complexes that assist in the folding of substrate proteins in an ATP-dependent reaction cycle. Key ...Chaperonins are ubiquitous molecular chaperones found in all domains of life. They form ring-shaped complexes that assist in the folding of substrate proteins in an ATP-dependent reaction cycle. Key to the folding cycle is the transient encapsulation of substrate proteins by the chaperonin. Here we present a structural and functional characterization of the chaperonin gp146 (ɸEL) from the phage EL of Pseudomonas aeruginosa. ɸEL, an evolutionarily distant homolog of bacterial GroEL, is active in ATP hydrolysis and prevents the aggregation of denatured protein in a nucleotide-dependent manner. However, ɸEL failed to refold the encapsulation-dependent model substrate rhodanese and did not interact with E. coli GroES, the lid-shaped co-chaperone of GroEL. ɸEL forms tetradecameric double-ring complexes, which dissociate into single rings in the presence of ATP. Crystal structures of ɸEL (at 3.54 and 4.03 Å) in presence of ATP•BeFx revealed two distinct single-ring conformational states, both with open access to the ring cavity. One state showed uniform ATP-bound subunit conformations (symmetric state), whereas the second combined distinct ATP- and ADP-bound subunit conformations (asymmetric state). Cryo-electron microscopy of apo-ɸEL revealed a double-ring structure composed of rings in the asymmetric state (3.45 Å resolution). We propose that the phage chaperonin undergoes nucleotide-dependent conformational switching between double- and single rings and functions in aggregation prevention without substrate protein encapsulation. Thus, ɸEL may represent an evolutionarily more ancient chaperonin prior to acquisition of the encapsulation mechanism.