@article{b8d4ddc8eb4042ab85eb68c6cbd100a6,
title = "Crystal structures of dimeric and heptameric mtHsp60 reveal the mechanism of chaperonin inactivation",
abstract = "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.",
author = "Lai, {Meng Cheng} and Cheng, {Hao Yu} and Lew, {Sin Hong} and Chen, {Yu An} and Yu, {Chien Hung} and Lin, {Han You} and Lin, {Shih Ming}",
note = "Funding Information: We appreciate the experimental facility and the technical services provided by the Synchrotron Radiation Protein Crystallography Core Facility (SPXF) of the National Core Facility for Biopharmaceuticals (NCFB), Ministry of Science and Technology (MOST), and the National Synchrotron Radiation Research Center (NSRRC), a national user facility funded by the Ministry of Science and Technology (MOST), Taiwan (R.O.C.). Initial crystallization screening was carried out at the NSRRC-NCKU Protein Crystallography Laboratory at University Center for Bioscience and Biotechnology of National Cheng Kung University (funding by NSRRC 11123LAB02). We gratefully acknowledge the use of TEM instruments (EM000900 of MOST 110-2731-M-006-001) belonging to the Core Facility Center of National Cheng Kung University. We would like to acknowledge funding from the Ministry of Science and Technology (MOST) of Taiwan (MOST 109-2636-B-006 -012; MOST 110-2636-B-006 -012; MOST 111-2636-B-006 -012) to S-M Lin. Publisher Copyright: {\textcopyright} 2023 Lai et al.",
year = "2023",
doi = "10.26508/lsa.202201753",
language = "English",
volume = "6",
journal = "Life Science Alliance",
issn = "2575-1077",
publisher = "Rockefeller University Press",
number = "6",
}