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The N-terminal domain plays a crucial role in the structure of a full-length human mitochondrial Lon protease
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SYSNO ASEP 0465343 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title The N-terminal domain plays a crucial role in the structure of a full-length human mitochondrial Lon protease Author(s) Kereiche, S. (CZ)
Kováčik, L. (CZ)
Bednár, J. (CZ)
Pevala, V. (SK)
Kunová, N. (SK)
Ondrovičová, G. (SK)
Bauer, J. (SK)
Ambro, L. (SK)
Bellová, J. (SK)
Kutejová, Eva (MBU-M) RID
Raška, I. (CZ)Source Title Scientific Reports. - : Nature Publishing Group - ISSN 2045-2322
Roč. 6, SEP 16 (2016), s. 33631Number of pages 10 s. Language eng - English Country GB - United Kingdom Keywords ESCHERICHIA-COLI LON ; SUBSTRATE TRANSLOCATION ; PROTEOLYTIC MACHINE Subject RIV EE - Microbiology, Virology R&D Projects ED1.1.00/02.0109 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) Institutional support MBU-M - RVO:61388971 UT WOS 000383651300001 EID SCOPUS 84987984594 DOI 10.1038/srep33631 Annotation on is an essential, multitasking AAA(+) protease regulating many cellular processes in species across all kingdoms of life. Altered expression levels of the human mitochondrial Lon protease (hLon) are linked to serious diseases including myopathies, paraplegia, and cancer. Here, we present the first 3D structure of full-length hLon using cryo-electron microscopy. hLon has a unique three-dimensional structure, in which the proteolytic and ATP-binding domains (AP-domain) form a hexameric chamber, while the N-terminal domain is arranged as a trimer of dimers. These two domains are linked by a narrow trimeric channel composed likely of coiled-coil helices. In the presence of AMP-PNP, the AP-domain has a closed-ring conformation and its N-terminal entry gate appears closed, but in ADP binding, it switches to a lock-washer conformation and its N-terminal gate opens, which is accompanied by a rearrangement of the N-terminal domain. We have also found that both the enzymatic activities and the 3D structure of a hLon mutant lacking the first 156 amino acids are severely disturbed, showing that hLon's N-terminal domains are crucial for the overall structure of the hLon, maintaining a conformation allowing its proper functioning. Workplace Institute of Microbiology Contact Eliška Spurná, eliska.spurna@biomed.cas.cz, Tel.: 241 062 231 Year of Publishing 2017
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