RT Journal Article
SR Electronic
T1 Crystal structures of dimeric and heptameric mtHsp60 reveal the mechanism of chaperonin inactivation
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e202201753
DO 10.26508/lsa.202201753
VO 6
IS 6
A1 Meng-Cheng Lai
A1 Hao-Yu Cheng
A1 Sin-Hong Lew
A1 Yu-An Chen
A1 Chien-Hung Yu
A1 Han-You Lin
A1 Shih-Ming Lin
YR 2023
UL https://www.life-science-alliance.org/content/6/6/e202201753.abstract
AB Mitochondrial Hsp60 (mtHsp60) plays a crucial role in maintaining the proper folding of proteins in the mitochondria. mtHsp60 self-assembles into a ring-shaped heptamer, which can further form a double-ring tetradecamer in the presence of ATP and mtHsp10. However, mtHsp60 tends to dissociate in vitro, unlike its prokaryotic homologue, GroEL. The molecular structure of dissociated mtHsp60 and the mechanism behind its dissociation remain unclear. In this study, we demonstrated that Epinephelus coioides mtHsp60 (EcHsp60) can form a dimeric structure with inactive ATPase activity. The crystal structure of this dimer reveals symmetrical subunit interactions and a rearranged equatorial domain. The α4 helix of each subunit extends and interacts with its adjacent subunit, leading to the disruption of the ATP-binding pocket. Furthermore, an RLK motif in the apical domain contributes to stabilizing the dimeric complex. These structural and biochemical findings provide new insights into the conformational transitions and functional regulation of this ancient chaperonin.