Insights from Bacterial Subtilases into the Mechanisms of Intramolecular Chaperone-Mediated Activation of Furin

Shinde, Ujwal; Thomas, Gary

doi:10.1007/978-1-61779-204-5_4

Cited by 62 publications

(117 citation statements)

References 125 publications

Supporting

Mentioning

111

Contrasting

Order By: Relevance

“…Much work has been done on the subtilase family of proteases, and prior work has led to the identification of the residues important for catalysis, and the identification of these residues is based on surrounding sequence motifs (83,84). Subtilases are commonly produced as a proenzyme in which the prodomain is autocatalytically removed to activate the protease (83,(85)(86)(87)(88). In C. perfringens, these three proteins are predicted activate the SCLE SleC.…”

Section: Csp-type Germinant Receptorsmentioning

confidence: 99%

Germinants and Their Receptors in Clostridia

2016

View full text Add to dashboard Cite

Many anaerobic spore-forming clostridial species are pathogenic, and some are industrially useful. Although many are strict anaerobes, the bacteria persist under aerobic and growth-limiting conditions as multilayered metabolically dormant spores. For many pathogens, the spore form is what most commonly transmits the organism between hosts. After the spores are introduced into the host, certain proteins (germinant receptors) recognize specific signals (germinants), inducing spores to germinate and subsequently grow into metabolically active cells. Upon germination of the spore into the metabolically active vegetative form, the resulting bacteria can colonize the host and cause disease due to the secretion of toxins from the cell. Spores are resistant to many environmental stressors, which make them challenging to remove from clinical environments. Identifying the conditions and the mechanisms of germination in toxin-producing species could help develop affordable remedies for some infections by inhibiting germination of the spore form. Unrelated to infectious disease, spore formation in species used in the industrial production of chemicals hinders the optimum production of the chemicals due to the depletion of the vegetative cells from the population. Understanding spore germination in acetone-butanol-ethanol-producing species can help boost the production of chemicals, leading to cheaper ethanol-based fuels. Until recently, clostridial spore germination is assumed to be similar to that of Bacillus subtilis. However, recent studies in Clostridium difficile shed light on a mechanism of spore germination that has not been observed in any endospore-forming organisms to date. In this review, we focus on the germinants and the receptors recognizing these germinants in various clostridial species.

show abstract

Section: Csp-type Germinant Receptorsmentioning

confidence: 99%

Germinants and Their Receptors in Clostridia

2016

View full text Add to dashboard Cite

show abstract

“…5). In the absence of further structural information, it is difficult to assess which structural changes could take place on calcium binding and cleavage at the primary maturation site.…”

Section: Post 3′ Utr Pbsub1mentioning

confidence: 99%

“…Functions range from unspecific hydrolysis of substrates in the environment generating free amino acids as nutriments in bacteria, to precise maturation of inactive precursors into active polypeptides, such as the tightly regulated pro-hormone to hormone conversion in eukaryotes [1][2][3] . Subtilases are synthesized as an inactive precursor, the zymogen, which is characterized by the presence of a prodomain that plays a dual essential role of intramolecular chaperone and specific inhibitor of the cognate catalytic domain 4,5 . During secretion, the prodomain undergoes an autoprocessing maturation process before to be degraded, thus unlocking enzymatic activity.…”

mentioning

confidence: 99%

“…Recent data have elegantly shown that the organelle-specific, pHdependent activation of the mammalian subtilases furin and PC1/3 along their secretion route is regulated in a prodomaindependent way 6 . The finely tuned spatiotemporal regulation of subtilases prevents intracellular damage caused by prematurely activated bacterial enzymes and allows pro-protein convertases (PC) to mature their substrates in ad hoc cellular compartments in response to a specific stimulus 2,3,5,7 .…”

mentioning

confidence: 99%

See 1 more Smart Citation

A novel Plasmodium-specific prodomain fold regulates the malaria drug target SUB1 subtilase

et al. 2014

View full text Add to dashboard Cite

The Plasmodium subtilase SUB1 plays a pivotal role during the egress of malaria parasites from host hepatocytes and erythrocytes. Here we report the crystal structure of full-length SUB1 from the human-infecting parasite Plasmodium vivax, revealing a bacterial-like catalytic domain in complex with a Plasmodium-specific prodomain. The latter displays a novel architecture with an amino-terminal insertion that functions as a 'belt', embracing the catalytic domain to further stabilize the quaternary structure of the pre-protease, and undergoes calcium-dependent autoprocessing during subsequent activation. Although dispensable for recombinant enzymatic activity, the SUB1 'belt' could not be deleted in Plasmodium berghei, suggesting an essential role of this domain for parasite development in vivo. The SUB1 structure not only provides a valuable platform to develop new anti-malarial candidates against this promising drug target, but also defines the Plasmodium-specific 'belt' domain as a key calcium-dependent regulator of SUB1 during parasite egress from host cells.

show abstract

“…3C), suggesting that the maturation of SptC* proceeds autocatalytically. In addition, the N-terminal propeptide deletion mutant SptC⌬N was unable to mature (data not shown), suggesting that the N-terminal propeptide acts as an intramolecular chaperone to assist enzyme folding, as in other subtilases (34).…”

Section: Resultsmentioning

confidence: 97%

Chitin Accelerates Activation of a Novel Haloarchaeal Serine Protease That Deproteinizes Chitin-Containing Biomass

Zhang

Wang

et al. 2014

Appl Environ Microbiol

View full text Add to dashboard Cite

bThe haloarchaeon Natrinema sp. strain J7-2 has the ability to degrade chitin, and its genome harbors a chitin metabolism-related gene cluster that contains a halolysin gene, sptC. The sptC gene encodes a precursor composed of a signal peptide, an N-terminal propeptide consisting of a core domain (N*) and a linker peptide, a subtilisin-like catalytic domain, a polycystic kidney disease domain (PkdD), and a chitin-binding domain (ChBD). Here we report that the autocatalytic maturation of SptC is initiated by cis-processing of N* to yield an autoprocessed complex (N*-I WT ), followed by trans-processing/degradation of the linker peptide, the ChBD, and N*. The resulting mature form (M WT ) containing the catalytic domain and the PkdD showed optimum azocaseinolytic activity at 3 to 3.5 M NaCl, demonstrating salt-dependent stability. Deletion analysis revealed that the PkdD did not confer extra stability on the enzyme but did contribute to enzymatic activity. The ChBD exhibited salt-dependent chitinbinding capacity and mediated the binding of N*-I WT to chitin. ChBD-mediated chitin binding enhances SptC maturation by promoting activation of the autoprocessed complex. Our results also demonstrate that SptC is capable of removing proteins from shrimp shell powder (SSP) at high salt concentrations. Interestingly, N*-I WT released soluble peptides from SSP faster than did M WT . Most likely, ChBD-mediated binding of the autoprocessed complex to chitin in SSP not only accelerates enzyme activation but also facilitates the deproteinization process by increasing the local protease concentration around the substrate. By virtue of these properties, SptC is highly attractive for use in preparation of chitin from chitin-containing biomass.

show abstract

Insights from Bacterial Subtilases into the Mechanisms of Intramolecular Chaperone-Mediated Activation of Furin

Cited by 62 publications

References 125 publications

Germinants and Their Receptors in Clostridia

Germinants and Their Receptors in Clostridia

A novel Plasmodium-specific prodomain fold regulates the malaria drug target SUB1 subtilase

Chitin Accelerates Activation of a Novel Haloarchaeal Serine Protease That Deproteinizes Chitin-Containing Biomass

Contact Info

Product

Resources

About