Structure and Mechanism of Rhomboid Protease

Ha, Ya; Akiyama, Yoshinori; Xue, Yi

doi:10.1074/jbc.r112.422378

Cited by 34 publications

(23 citation statements)

References 63 publications

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“…Insertion-deletion mutations in comEB and rbd were generated and the synthetic lethality upon depletion of Noc was confirmed ( Fig 1B ). The rbd gene encodes a member of the Rhomboid family of membrane-embedded serine proteases [ 21 , 22 ]. ComEB is homologous to deoxycytidylate deaminase, an enzyme in one of the dTTP synthesis pathways [ 23 ].…”

Section: Resultsmentioning

confidence: 99%

The nucleoid occlusion factor Noc controls DNA replication initiation in Staphylococcus aureus

et al. 2017

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Successive division events in the spherically shaped bacterium Staphylococcus aureus are oriented in three alternating perpendicular planes. The mechanisms that underlie this relatively unique pattern of division and coordinate it with chromosome segregation remain largely unknown. Thus far, the only known spatial regulator of division in this organism is the nucleoid occlusion protein Noc that inhibits assembly of the cytokinetic ring over the chromosome. However, Noc is not essential in S. aureus, indicating that additional regulators are likely to exist. To search for these factors, we screened for mutants that are synthetic lethal with Noc inactivation. Our characterization of these mutants led to the discovery that S. aureus Noc also controls the initiation of DNA replication. We show that cells lacking Noc over-initiate and mutations in the initiator gene dnaA suppress this defect. Importantly, these dnaA mutations also partially suppress the division problems associated with Δnoc. Reciprocally, we show that over-expression of DnaA enhances the over-initiation and cell division phenotypes of the Δnoc mutant. Thus, a single factor both blocks cell division over chromosomes and helps to ensure that new rounds of DNA replication are not initiated prematurely. This degree of economy in coordinating key cell biological processes has not been observed in rod-shaped bacteria and may reflect the challenges posed by the reduced cell volume and complicated division pattern of this spherical pathogen.

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Section: Resultsmentioning

confidence: 99%

The nucleoid occlusion factor Noc controls DNA replication initiation in Staphylococcus aureus

et al. 2017

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“…The protease was shown to be involved in activation of epidermal growth factor receptor (EGFR) ligands. A mutation within the gene encoding the protein resulted in skeleton deformations in Drosophila larvae, leading to a characteristic ''rhombus-like'' shape of their heads (Ha et al 2013).…”

Section: Rhomboids In a Thalianamentioning

confidence: 99%

Arabidopsis thaliana intramembrane proteases

et al. 2017

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Proteolysis is considered as a crucial factor determining the proper development of the plant and its efficient functioning in variable environmental conditions. The role of proteases in protein quality control and protein turnover processes is well documented. The results of studies performed in recent years reveal; however, that proteolytic enzymes also participate in signal transduction pathways by releasing membrane-anchored transcription factors in the process known as regulated intramembrane proteolysis (RIP). The first described intramembrane protease was identified in human cells in 1997. In turn, the first plant intramembrane protease was identified in 2005, in Arabidopsis thaliana. To date, most studies concerning the RIP process in plants have been performed on this model plant. The knowledge concerning the potential physiological role of RIP is very limited. However, continuously accumulating information concerning this issue indicates that RIP, like the other proteolytic mechanisms, has a significant effect on plant ontogenesis, acclimatization and fertility. The aim of this article is to gather and systemize the present knowledge concerning the intramembrane proteases in A. thaliana.

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“…More recently it has been shown that some rhomboid proteases can cleave sequences within hydrophilic sequences outside of transmembrane domains [42][43][44]. In these cases, the hydrophilic peptide substrates bend into the protease active site from above the membrane plane (reviewed in [48]). Our observations suggest the EhROM1 may also be capable of cleaving sequences outside of the membrane environment.…”

Section: Plos Onementioning

confidence: 99%

“…Along with Trichomonas vaginalis ROM1 (TvROM1) [30] and Plasmodium falciparum Rhomboid 4 (PfROM4) [27], EhROM1 is one of three parasite rhomboid proteases that cannot process Spitz, a substrate from Drosophila that is cleaved by most known rhomboid proteases [31]. A variety of processes for rhomboid-substrate recognition seem to exist [48]. For instance, cleavage of thrombomodulin by vertebrate rhomboid-2, RHBDL2, is directed by the substrate's cytoplasmic tail rather than by sequences in its transmembrane region [52].…”

Section: Plos Onementioning

confidence: 99%

Reduced expression of a rhomboid protease, EhROM1, correlates with changes in the submembrane distribution and size of the Gal/GalNAc lectin subunits in the human protozoan parasite, Entamoeba histolytica

2020

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Entamoeba histolytica is a food-and waterborne parasite that causes amebic dysentery and amoebic liver abscesses. Adhesion is one of the most important virulence functions as it facilitates motility, colonization of host, destruction of host tissue, and uptake of nutrients by the parasite. The parasite cell surface adhesin, the Gal/GalNAc lectin, facilitates parasitehost interaction by binding to galactose or N-acetylgalactosamine residues on host components. It is composed of heavy (Hgl), intermediate (Igl), and light (Lgl) subunits. Igl is constitutively localized to lipid rafts (cholesterol-rich membrane domains), whereas Hgl and Lgl transiently associate with rafts. When all three subunits are localized to rafts, galactose-sensitive adhesion is enhanced. Thus, submembrane location may regulate the function of this adhesion. Rhomboid proteases are a conserved family of intramembrane proteases that also participate in the regulation of parasite-host interactions. In E. histolytica, one rhomboid protease, EhROM1, cleaves Hgl as a substrate, and knockdown of its expression inhibits parasite-host interactions. Since rhomboid proteases are found within membranes, it is not surprising that lipid composition regulates their activity and enzyme-substrate binding. Given the importance of the lipid environment for both rhomboid proteases and the Gal/Gal-NAc lectin, we sought to gain insight into the relationship between rhomboid proteases and submembrane location of the lectin in E. histolytica. We demonstrated that EhROM1, itself, is enriched in highly buoyant triton-insoluble membranes reminiscent of rafts. Reducing rhomboid protease activity, either pharmacologically or genetically, correlated with an enrichment of Hgl and Lgl in rafts. In a mutant cell line with reduced EhROM1 expression, there was also a significant augmentation of the level of all three Gal/GalNAc subunits on the cell surface and an increase in the molecular weight of Hgl and Lgl. Overall, the study provides insight into the molecular mechanisms governing parasite-host adhesion for this pathogen.

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Structure and Mechanism of Rhomboid Protease

Cited by 34 publications

References 63 publications

The nucleoid occlusion factor Noc controls DNA replication initiation in Staphylococcus aureus

The nucleoid occlusion factor Noc controls DNA replication initiation in Staphylococcus aureus

Arabidopsis thaliana intramembrane proteases

Reduced expression of a rhomboid protease, EhROM1, correlates with changes in the submembrane distribution and size of the Gal/GalNAc lectin subunits in the human protozoan parasite, Entamoeba histolytica

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