4YPM

Crystal structure of a LonA protease domain in complex with bortezomib

Summary for 4YPM

• Entry DOI: 10.2210/pdb4ypm/pdb
• Related: 4YPL 4YPN
• Descriptor: Lon protease, N-[(1R)-1-(DIHYDROXYBORYL)-3-METHYLBUTYL]-N-(PYRAZIN-2-YLCARBONYL)-L-PHENYLALANINAMIDE, MAGNESIUM ION, ... (6 entities in total)
• Functional Keywords: aaa+ domain, lon protease, protease domain, magnesium, bortezomib, hydrolase
• Biological source: Meiothermus taiwanensis
• Cellular location: Cytoplasm : A0A059VAZ3
• Total number of polymer chains: 1
• Total formula weight: 33531.27

Authors

Lin, C.-C.,Chang, C.-I. (deposition date: 2015-03-13, release date: 2016-03-16, Last modification date: 2024-10-16)

Primary citation

Su, S.-C.,Lin, C.-C.,Tai, H.-C.,Chang, M.-Y.,Ho, M.-R.,Babu, C.S.,Liao, J.-H.,Wu, S.-H.,Chang, Y.-C.,Lim, C.,Chang, C.-I.
Structural Basis for the Magnesium-Dependent Activation and Hexamerization of the Lon AAA+ Protease
Structure, 24:676-686, 2016

PubMed Abstract: The Lon AAA+ protease (LonA) plays important roles in protein homeostasis and regulation of diverse biological processes. LonA behaves as a homomeric hexamer in the presence of magnesium (Mg(2+)) and performs ATP-dependent proteolysis. However, it is also found that LonA can carry out Mg(2+)-dependent degradation of unfolded protein substrate in an ATP-independent manner. Here we show that in the presence of Mg(2+) LonA forms a non-secluded hexameric barrel with prominent openings, which explains why Mg(2+)-activated LonA can operate as a diffusion-based chambered protease to degrade unstructured protein and peptide substrates efficiently in the absence of ATP. A 1.85 Å crystal structure of Mg(2+)-activated protease domain reveals Mg(2+)-dependent remodeling of a substrate-binding loop and a potential metal-binding site near the Ser-Lys catalytic dyad, supported by biophysical binding assays and molecular dynamics simulations. Together, these findings reveal the specific roles of Mg(2+) in the molecular assembly and activation of LonA.

PubMed: 27041593
DOI: 10.1016/j.str.2016.03.003

Experimental method

X-RAY DIFFRACTION (1.85 Å)