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Query: EC:3.6.1.3 (ATPase)
 65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

All organisms must adapt to ever-changing environmental conditions and accordingly have evolved diverse signal transduction systems. In bacteria, the most abundant networks are built around the two-component signal transduction systems that include histidine kinases and receiver domains. In contrast, eukaryotic signal transduction is dominated by serine/threonine/tyrosine protein kinases. Both of these systems are also found in archaea, but they are not as common and diversified as their bacterial and eukaryotic counterparts, suggesting the possibility that archaea have evolved other, still uncharacterized signal transduction networks. Here we propose a role for KaiC family ATPases, known to be key components of the circadian clock in cyanobacteria, in archaeal signal transduction. The KaiC family is notably expanded in most archaeal genomes, and although most of these ATPases remain poorly characterized, members of the KaiC family have been shown to control archaellum assembly and have been found to be a stable component of the gas vesicle system in Halobacteria Computational analyses described here suggest that KaiC-like ATPases and their homologues with inactivated ATPase domains are involved in many other archaeal signal transduction pathways and comprise major hubs of complex regulatory networks. We predict numerous input and output domains that are linked to KaiC-like proteins, including putative homologues of eukaryotic DEATH domains that could function as adapters in archaeal signaling networks. We further address the relationships of the archaeal family of KaiC homologues to the bona fide KaiC of cyanobacteria and implications for the existence of a KaiC-based circadian clock apparatus in archaea.IMPORTANCE Little is currently known about signal transduction pathways in Archaea Recent studies indicate that KaiC-like ATPases, known as key components of the circadian clock apparatus in cyanobacteria, are involved in the regulation of archaellum assembly and, likely, type IV pili and the gas vesicle system in Archaea We performed comprehensive comparative genomic analyses of the KaiC family. A vast protein interaction network was revealed, with KaiC family proteins as hubs for numerous input and output components, many of which are shared with two-component signal transduction systems. Putative KaiC-based signal transduction systems are predicted to regulate the activities of membrane-associated complexes and individual proteins, such as signal recognition particle and membrane transporters, and also could be important for oxidative stress response regulation. KaiC-centered signal transduction networks are predicted to play major roles in archaeal physiology, and this work is expected to stimulate their experimental characterization.
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PMID:Proposed Role for KaiC-Like ATPases as Major Signal Transduction Hubs in Archaea. 2920 47

About 30% of all bacterial proteins execute their function outside of the cytosol and have to be transported into or across the cytoplasmic membrane. Bacteria use multiple protein transport systems in parallel, but the majority of proteins engage two distinct targeting systems. One is the co-translational targeting by two universally conserved GTPases, the signal recognition particle (SRP) and its receptor FtsY, which deliver inner membrane proteins to either the SecYEG translocon or the YidC insertase for membrane insertion. The other targeting system depends on the ATPase SecA, which targets secretory proteins, i.e. periplasmic and outer membrane proteins, to SecYEG for their subsequent ATP-dependent translocation. While SRP selects its substrates already very early during their synthesis, the recognition of secretory proteins by SecA is believed to occur primarily after translation termination, i.e. post-translationally. In this review we highlight recent progress on how SRP recognizes its substrates at the ribosome and how the fidelity of the targeting reaction to SecYEG is maintained. We furthermore discuss similarities and differences in the SRP-dependent targeting to either SecYEG or YidC and summarize recent results that suggest that some membrane proteins are co-translationally targeted by SecA.
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PMID:Co-translational protein targeting in bacteria. 2979 Sep 84

Many proteins must translocate through the protein-conducting Sec61 channel in the eukaryotic endoplasmic reticulum membrane or the SecY channel in the prokaryotic plasma membrane1,2. Proteins with highly hydrophobic signal sequences are first recognized by the signal recognition particle (SRP)3,4 and then moved co-translationally through the Sec61 or SecY channel by the associated translating ribosome. Substrates with less hydrophobic signal sequences bypass the SRP and are moved through the channel post-translationally5,6. In eukaryotic cells, post-translational translocation is mediated by the association of the Sec61 channel with another membrane protein complex, the Sec62-Sec63 complex7-9, and substrates are moved through the channel by the luminal BiP ATPase9. How the Sec62-Sec63 complex activates the Sec61 channel for post-translational translocation is not known. Here we report the electron cryo-microscopy structure of the Sec complex from Saccharomyces cerevisiae, consisting of the Sec61 channel and the Sec62, Sec63, Sec71 and Sec72 proteins. Sec63 causes wide opening of the lateral gate of the Sec61 channel, priming it for the passage of low-hydrophobicity signal sequences into the lipid phase, without displacing the channel's plug domain. Lateral channel opening is triggered by Sec63 interacting both with cytosolic loops in the C-terminal half of Sec61 and transmembrane segments in the N-terminal half of the Sec61 channel. The cytosolic Brl domain of Sec63 blocks ribosome binding to the channel and recruits Sec71 and Sec72, positioning them for the capture of polypeptides associated with cytosolic Hsp7010. Our structure shows how the Sec61 channel is activated for post-translational protein translocation.
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PMID:Structure of the post-translational protein translocation machinery of the ER membrane. 3096 27

More than a third of all bacterial polypeptides, comprising the 'exportome', are transported to extracytoplasmic locations. Most of the exportome is targeted and inserts into ('membranome') or crosses ('secretome') the plasma membrane. The membranome and secretome use distinct targeting signals and factors, and driving forces, but both use the ubiquitous and essential Sec translocase and its SecYEG protein-conducting channel. Membranome export is co-translational and uses highly hydrophobic N-terminal signal anchor sequences recognized by the signal recognition particle on the ribosome, that also targets C-tail anchor sequences. Translating ribosomes drive movement of these polypeptides through the lateral gate of SecY into the inner membrane. On the other hand, secretome export is post-translational and carries two types of targeting signals: cleavable N-terminal signal peptides and multiple short hydrophobic targeting signals in their mature domains. Secretome proteins remain translocation competent due to occupying loosely folded to completely non-folded states during targeting. This is accomplished mainly by the intrinsic properties of mature domains and assisted by signal peptides and/or chaperones. Secretome proteins bind to the dimeric SecA subunit of the translocase. SecA converts from a dimeric preprotein receptor to a monomeric ATPase motor and drives vectorial crossing of chains through SecY aided by the proton motive force. Signal peptides are removed by signal peptidases and translocated chains fold or follow subsequent trafficking.
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PMID:Protein Transport Across the Bacterial Plasma Membrane by the Sec Pathway. 3113 61

Bacteria execute a variety of protein transport systems for maintaining the proper composition of their different cellular compartments. The SecYEG translocon serves as primary transport channel and is engaged in transporting two different substrate types. Inner membrane proteins are cotranslationally inserted into the membrane after their targeting by the signal recognition particle (SRP). In contrast, secretory proteins are posttranslationally translocated by the ATPase SecA. Recent data indicate that SecA can also bind to ribosomes close to the tunnel exit. We have mapped the interaction of SecA with translating and nontranslating ribosomes and demonstrate that the N terminus and the helical linker domain of SecA bind to an acidic patch on the surface of the ribosomal protein uL23. Intriguingly, both also insert deeply into the ribosomal tunnel to contact the intratunnel loop of uL23, which serves as a nascent chain sensor. This binding pattern is remarkably similar to that of SRP and indicates an identical interaction mode of the two targeting factors with ribosomes. In the presence of a nascent chain, SecA retracts from the tunnel but maintains contact with the surface of uL23. Our data further demonstrate that ribosome and membrane binding of SecA are mutually exclusive, as both events depend on the N terminus of SecA. Our study highlights the enormous plasticity of bacterial protein transport systems and reveals that the discrimination between SRP and SecA substrates is already initiated at the ribosome.IMPORTANCE Bacterial protein transport via the conserved SecYEG translocon is generally classified as either cotranslational, i.e., when transport is coupled to translation, or posttranslational, when translation and transport are separated. We show here that the ATPase SecA, which is considered to bind its substrates posttranslationally, already scans the ribosomal tunnel for potential substrates. In the presence of a nascent chain, SecA retracts from the tunnel but maintains contact with the ribosomal surface. This is remarkably similar to the ribosome-binding mode of the signal recognition particle, which mediates cotranslational transport. Our data reveal a striking plasticity of protein transport pathways, which likely enable bacteria to efficiently recognize and transport a large number of highly different substrates within their short generation time.
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PMID:Molecular Mimicry of SecA and Signal Recognition Particle Binding to the Bacterial Ribosome. 3179 25

The ribosome is a sophisticated cellular machine, composed of RNA and protein, which translates the mRNA-encoded genetic information into protein and thus acts at the center of gene expression. Still, the ribosome not only decodes the genetic information, it also coordinates many ribosome-associated processes like protein folding and targeting. The ribosomal protein uL23 is crucial for this coordination and is located at the ribosomal tunnel exit where it serves as binding platform for targeting factors, chaperones and modifying enzymes. This includes the signal recognition particle (SRP), which facilitates co-translational protein targeting in pro- and eukaryotes, the chaperone Trigger Factor and methionine aminopeptidase, which removes the start methionine in many bacterial proteins. A recent report revealed the intricate interaction of uL23 with yet another essential player in bacteria, the ATPase SecA, which is best known for its role during post-translational secretion of proteins across the bacterial SecYEG translocon.
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PMID:Yet another job for the bacterial ribosome. 3140 76

Some bacterial species, such as the marine bacterium Vibrio alginolyticus, have a single polar flagellum that allows it to swim in liquid environments. Two regulators, FlhF and FlhG, function antagonistically to generate only one flagellum at the cell pole. FlhF, a signal recognition particle (SRP)-type guanosine triphosphate (GTP)ase, works as a positive regulator for flagellar biogenesis and determines the location of flagellar assembly at the pole, whereas FlhG, a MinD-type ATPase, works as a negative regulator that inhibits flagellar formation. FlhF intrinsically localizes at the cell pole, and guanosine triphosphate (GTP) binding to FlhF is critical for its polar localization and flagellation. FlhG also localizes at the cell pole via the polar landmark protein HubP to directly inhibit FlhF function at the cell pole, and this localization depends on ATP binding to FlhG. However, the detailed regulatory mechanisms involved, played by FlhF and FlhG as the major factors, remain largely unknown. This article reviews recent studies that highlight the post-translational regulation mechanism that allows the synthesis of only a single flagellum at the cell pole.
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PMID:Regulation of the Single Polar Flagellar Biogenesis. 3224 80


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