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Publication Abstract from PubMed

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 A 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.

Structural Basis for the Magnesium-Dependent Activation and Hexamerization of the Lon AAA+ Protease.,Su SC, Lin CC, Tai HC, Chang MY, Ho MR, Babu CS, Liao JH, Wu SH, Chang YC, Lim C, Chang CI Structure. 2016 May 3;24(5):676-86. doi: 10.1016/j.str.2016.03.003. Epub 2016 Mar, 31. PMID:27041593^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.