Lon and ClpP proteases participate in the physiological disintegration of bacterial inclusion bodies

Protein aggregation in bacteria: the thin boundary between functionality and toxicity

“…The physiological disassembly of IBs is directed by Lon ATP-dependent protease and ClpP protease. The disaggregation process is started by Lon, which recognizes specific hydrophobic and aromatic stretches in damaged proteins, followed by ClpP binding of the released, reversibly misfolded proteins (Vera et al, 2005).…”

“…At low magnification, all IBs share a common structure; they are very condensed, insoluble particles that can be found in both the cytoplasmic and periplasmic space of bacteria. Originally, IBs were considered as non-specific protein aggregates; however, deeper insight into their morphology showed that bacterial IBs display amyloid-like properties (Carrió et al, 2005). The structural data suggest that newly formed b-sheet architecture in IBs is stabilized by a network of hydrogen bonds, resulting in tightly packed, extended intermolecular b-sheets (Ventura & Villaverde, 2006).…”

Inclusion body anatomy and functioning of chaperone-mediated in vivo inclusion body disassembly during high-level recombinant protein production in Escherichia coli

“…They have long been regarded as a localized mass of unordered polypeptide chains but more recent research suggested that these proteins may also have defined conformations within the aggregated state (Ventura and Villaverde, 2006). Inclusion bodies also have long 5 been considered inert towards in vivo dissolution, but it is now generally accepted that inclusion body proteins can be solubilized in vivo concomitant to or followed by proteolytic degradation (Corchero et al, 1997, Carrió et al, 1999Cubarsí et al, 2001;LeThanh et al, 2005;Vera et al, 2005) or even by folding into the native state LeThanh et al, 2005). 10 Comparable observations have been made with endogenous proteins aggregated by heatshock in E. coli which resolubilize when cells are subjected to lower temperature (Kędzierska et al, 1999).…”

Targeted Protein Degradation by Salmonella under Phagosome-mimicking Culture Conditions Investigated Using Comparative Peptidomics

“…These extensions are probably structurally disordered when unbound to polynucleotides because they are disproportionately detected by proteome-wide predictions of regions of intrinsic structural disorder (45,46). Lon is known to target defective proteins (47)(48)(49)(50)(51), probably because its unfoldase can process proteins that contain intrinsically disordered a These peptidomic samples are described in the Fig. 4 legend.…”

“…4, dnaK (33,50,65) and hns (33,66), are known to be carbonylated in response to starvation, and it is possible that they are subsequently targeted for proteolysis. Although Lon is the major protease of aberrant proteins in bacteria (47)(48)(49)(50)(51), ClpABPX (49 -51, 67), HslUV (50), and HtrA (49, 68) also have important roles. Therefore, two modes of protein degradation are likely upregulated by phagocytosed Salmonella, PolyP/Lon-dependent directed proteolysis of ribosomal proteins and ClpABPX/HslUV/ HtrA/Lon proteolysis of defective stress response factors.…”