PT  - JOURNAL ARTICLE
AU  - Meng-Cheng Lai
AU  - Hao-Yu Cheng
AU  - Sin-Hong Lew
AU  - Yu-An Chen
AU  - Chien-Hung Yu
AU  - Han-You Lin
AU  - Shih-Ming Lin
TI  - Crystal structures of dimeric and heptameric mtHsp60 reveal the mechanism of chaperonin inactivation
AID  - 10.26508/lsa.202201753
DP  - 2023 Jun 01
TA  - Life Science Alliance
PG  - e202201753
VI  - 6
IP  - 6
4099  - https://www.life-science-alliance.org/content/6/6/e202201753.short
4100  - https://www.life-science-alliance.org/content/6/6/e202201753.full
SO  - Life Sci. Alliance2023 Jun 01; 6
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.