The Lon AAA+ Protease
As the first ATP-dependent protease to be identified, Lon holds a special place in the history of cellular biology. In fact, the concept of ATP-dependent protein degradation was established through the findings that led to the discovery of Lon. Therefore,
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The Lon AAA+ Protease Eyal Gur
Abstract As the first ATP-dependent protease to be identified, Lon holds a special place in the history of cellular biology. In fact, the concept of ATP-dependent protein degradation was established through the findings that led to the discovery of Lon. Therefore, this chapter begins with a historical perspective, describing the milestones that led to the discovery of Lon and ATP-dependent proteolysis, starting from the early findings in the 1960s until the demonstration of Lon’s ATP-dependent proteolytic activity in vitro, in 1981. Most of our knowledge on Lon derives from studies of the Escherichia coli Lon ortholog, and, therefore, most of this chapter relates to this particular enzyme. Nonetheless, Lon is not only found in most bacterial species, it is also found in Archaea and in the mitochondrion and chloroplast of eukaryotic cells. Therefore many of the conclusions gained from studies on the E. coli enzyme are relevant to Lon proteases in other organisms. Lon, more than any other bacterial or organellar protease, is associated with the degradation of misfolded proteins and protein quality control. In addition, Lon also degrades many regulatory proteins that are natively folded, thus it also plays a prominent role in regulation of physiological processes. Throughout the years, many Lon substrates have been identified, confirming its role in the regulation of diverse cellular processes, including cell division, DNA replication, differentiation, and adaptation to stress conditions. Some examples of these functions are described and discussed here, as is the role of Lon in the degradation of misfolded proteins and in protein quality control. Finally, this chapter deals with the exquisite sensitivity of protein degradation inside a cell. How can a protease distinguish so many substrates from cellular proteins that
E. Gur (*) Life Sciences Department, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel Life Sciences Department, The National Institute for Biotechnology in the Negev, Beer-Sheva 84105, Israel e-mail: [email protected] D.A. Dougan (ed.), Regulated Proteolysis in Microorganisms, Subcellular Biochemistry 66, DOI 10.1007/978-94-007-5940-4_2, © Springer Science+Business Media Dordrecht 2013
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should not be degraded? Can the specificity of a protease be regulated according to the physiological needs of a cell? This chapter thus broadly discusses the substrate specificity of Lon and its allosteric regulation.
From the lac operon to the Discovery of ATP-Dependent Proteolysis In 1961 Francois Jacob and Jacques Monod made a major breakthrough in the biological sciences, as they presented their model of the lac operon and established the first paradigm for regulation of gene expression [1]. It was a brilliant, simple and coherent model that was based on negative regulation, i.e., on a repressor that binds to an operator region on the DNA and controls the expression of downstream genes. The model was readily accepted as a general mechanism for gene regulati
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