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Title | Structural Basis for the Magnesium-Dependent Activation and Hexamerization of the Lon AAA+ Protease. |
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Journal, issue, pages | Structure, Vol. 24, Issue 5, Page 676-686, Year 2016 |
Publish date | May 3, 2016 |
Authors | Shih-Chieh Su / Chien-Chu Lin / Hui-Chung Tai / Mu-Yueh Chang / Meng-Ru Ho / C Satheesan Babu / Jiahn-Haur Liao / Shih-Hsiung Wu / Yuan-Chih Chang / Carmay Lim / Chung-I Chang / |
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 ...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. |
External links | Structure / PubMed:27041593 |
Methods | EM (single particle) / X-ray diffraction |
Resolution | 1.85 - 12.6 Å |
Structure data | EMDB-6303: EMDB-6305: PDB-4ypm: PDB-5e7s: |
Chemicals | ChemComp-BO2: ChemComp-MG: ChemComp-PEG: ChemComp-CIT: ChemComp-HOH: |
Source |
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Keywords | HYDROLASE / AAA+ domain / Lon protease / protease domain / Magnesium / Bortezomib |