25 research outputs found
Discovery of the Lanthipeptide Curvocidinâ and Structural Insights into its Trifunctional Synthetase CuvL
Lanthipeptides are ribosomally-synthesized natural products from bacteria featuring stable thioether-crosslinks and various bioactivities. Herein, we report on a new clade of tricyclic class-IV lanthipeptides with curvocidin from Thermomonospora curvata as its first representative. We obtained crystal structures of the corresponding lanthipeptide synthetase CuvL that showed a circular arrangement of its kinase, lyase and cyclase domains, forming a central reaction chamber for the iterative substrate processing involving nine catalytic steps. The combination of experimental data and artificial intelligence-based structural models identified the N-terminal subdomain of the kinase domain as the primary site of substrate recruitment. The ribosomal precursor peptide of curvocidin employs an amphipathic α-helix in its leader region as an anchor to CuvL, while its substrate core shuttles within the central reaction chamber. Our study thus reveals general principles of domain organization and substrate recruitment of class-IV and class-III lanthipeptide synthetases.Deutsche Forschungsgemeinschaft
http://dx.doi.org/10.13039/501100001659Research Training Group RTG 2473 "Bioactive Peptides"RTG 2473 "Bioactive Peptides"Peer Reviewe
Oceanic response to Pliensbachian and Toarcian magmatic events: Implications from an organic-rich basinal succession in the NW Tethys
The BÀchental bituminous marls (BÀchentaler Bitumenmergel) belonging to the Sachrang Member of the Lower Jurassic Middle AllgÀu Formation were investigated using a multidisciplinary approach to determine environmental controls on the formation of organic-rich deposits in a semi-restricted basin of the NW Tethys during the Early Jurassic. The marls are subdivided into three units on the basis of mineralogical composition, source-rock parameters, redox conditions, salinity variations, and diagenetic processes. Redox proxies (e.g., pristane/phytane ratio; aryl isoprenoids; bioturbation; ternary plot of iron, total organic carbon, and sulphur) indicate varying suboxic to euxinic conditions during deposition of the BÀchental section. Redox variations were mainly controlled by sea-level fluctuations with the tectonically complex bathymetry of the BÀchental basin determining watermass exchange with the Tethys Ocean. Accordingly, strongest anoxia and highest total organic carbon content (up to 13%) occur in the middle part of the profile (upper tenuicostatum and lower falciferum zones), coincident with an increase in surface-water productivity during a period of relative sea-level lowstand that induced salinity stratification in a stagnant basin setting. This level corresponds to the time interval of the lower Toarcian oceanic anoxic event (T-OAE). However, the absence of the widely observed lower Toarcian negative carbon isotope excursion in the study section questions its unrestricted use as a global chemostratigraphic marker. Stratigraphic correlation of the thermally immature BÀchental bituminous marls with the Posidonia Shale of SW Germany on the basis of C27/C29 sterane ratio profiles and ammonite data suggests that deposition of organic matter-rich sediments in isolated basins in the Alpine realm commenced earlier (late Pliensbachian margaritatus Zone) than in regionally proximal epicontinental seas (early Toarcian tenuicostatum Zone). The late Pliensbachian onset of reducing conditions in the BÀchental basin coincided with an influx of volcaniclastic detritus that was possibly connected to complex rifting processes of the Alpine Tethys and with a globally observed eruption-induced extinction event. The level of maximum organic matter accumulation in the BÀchental basin corresponds to the main eruptive phase of the Karoo-Ferrar large igneous province (LIP), confirming its massive impact on global climate and oceanic conditions during the Early Jurassic. The BÀchental marl succession is thus a record of the complex interaction of global (i.e., LIP) and local (e.g., redox and salinity variations, basin morphology) factors that caused reducing conditions and organic matter enrichment in the BÀchental basin. These developments resulted in highly inhomogeneous environmental conditions in semi-restricted basins of the NW Tethyan domain during late Pliensbachian and early Toarcian time
Hop/Sti1 phosphorylation inhibits its co-chaperone function.
In eukaryotes, the molecular chaperones Hsp90 and Hsp70 are connected via the co-chaperone Sti1/Hop, which allows transfer of clients. Here, we show that the basic functions of yeast Sti1 and human Hop are conserved. These include the simultaneous binding of Hsp90 and Hsp70, the inhibition of the ATPase activity of Hsp90, and the ability to support client activation in vivo. Importantly, we reveal that both Hop and Sti1 are subject to inhibitory phosphorylation, although the sites modified and the influence of regulatory phosphorylation is species specific. Phospho-mimetic variants have a reduced ability to activate clients in vivo and different affinity for Hsp70. Hop is more tightly regulated, as phosphorylation affects also the interaction with Hsp90 and induces structural rearrangements in the core part of the protein
Hsp90 regulates the dynamics of its cochaperone Sti1 and the transfer of Hsp70 between modules.
The cochaperone Sti1/Hop physically links Hsp70 and Hsp90. The protein exhibits one binding site for Hsp90 (TPR2A) and two binding sites for Hsp70 (TPR1 and TPR2B). How these sites are used remained enigmatic. Here we show that Sti1 is a dynamic, elongated protein that consists of a flexible N-terminal module, a long linker and a rigid C-terminal module. Binding of Hsp90 and Hsp70 regulates the Sti1 conformation with Hsp90 binding determining with which site Hsp70 interacts. Without Hsp90, Sti1 is more compact and TPR2B is the high-affinity interaction site for Hsp70. In the presence of Hsp90, Hsp70 shifts its preference. The linker connecting the two modules is crucial for the interaction with Hsp70 and for client activation in vivo. Our results suggest that the interaction of Hsp70 with Sti1 is tightly regulated by Hsp90 to assure transfer of Hsp70 between the modules, as a prerequisite for the efficient client handover
Evidence for local carbonâcycle perturbations superimposed on the Toarcian carbon isotope excursion
A Jurassic negative carbon isotope excursion (CIE), co-evolved with Toarcian Oceanic Anoxic Event (OAE) at ~183 Ma, is suggested to be linked to a global carbon-cycle perturbation and is well documented for Toarcian terrestrial fossil woods and marine sediments around the globe. A theoretically coupled ÎŽ13Ccarb-ÎŽ13Corg pattern due to such dubbed global carbon-cycle event from the negative CIE in Dotternhausen Toarcian stratigraphic profile (southwest Germany) is unexpectedly disturbed by two-step ÎŽ13Ccarb-ÎŽ13Corg decoupling in which the last step, upper in the stratigraphic order, is of higher magnitude. However, the trigger(s) for these sudden decoupling disturbances are still poorly constrained. Here, connecting new carbon and oxygen isotope data with documentary lipid biomarkers shows that the global carbon cycle during the Toarcian OAE was disturbed by enhanced green sulfur bacteria (GSB) metabolisms and early diagenesis at local scales. The first step ÎŽ13Ccarb-ÎŽ13Corg decoupling was induced in the initial stage of the GSB bloom. The second step of much larger ÎŽ13Ccarb-ÎŽ13Corg decoupling arising from a GSB prosperity was, however, exaggerated by early diagenesis through the respiration of sulfate-reducing bacteria (SRB). Paleo-geographically distinct localities of the Tethys region show contrasting decoupled ÎŽ13Ccarb-ÎŽ13Corg patterns, which implies that the second-order carbon-cycle perturbations have pervasively and independently impacted the global carbon event during the Toarcian OAE
Microbially-mediated fossil-bearing carbonate concretions and their significance for palaeoenvironmental reconstructions: A multi-proxy organic and inorganic geochemical appraisal
Carbonate concretions are widespread within the geological record. However, the lack of recent known analogues creates a need for novel approaches to unravel the major microbial players involved in concretion formation and establish their suitability as palaeoenvironmental recorders. Here, we used a combination of geochemical and geological techniques to study two pyritiferous calcite concretions and compared the results with their host sediment (Toarcian âPosidonia Shaleâ, 183 Ma, SW-Germany). The 13C-depleted nature of the concretion bodies, with average values of d13Ccarb (-14.8â°), d13Corg (-32.4â°), and d13Cn-alkanes (-34.9â°), indicates that sulphate-reducing bacteria (SRB), played amajor role in the concretion growth and preservation of the nucleus via the rapid decomposition of organic matter (OM). However, Rock-Eval analyses from both concretions revealed elevated hydrogen indices (HI) in the body and lowHI values at the rim. These values suggest that most of the microbial activity did not occur in the concretion body but rather at the rim and at the surface of the nuclei, which generally supports the exceptional preservation of OM in carbonate concretions. Furthermore, enrichment in euhedral pyrite in the concretion rims suggests they were formed through increased activities of iron reducing (FeR) bacteria coupled to a decrease of SRB activity leading towards conditions more favourable to the direct precipitation of pyrite. Despite low d13C values, the known lipid biomarkers such as acyclic extended isoprenoids or 3Ă-methyl-hopanes did not reveal evidence of an active methane cycling. The present study emphasises the crucial role of carbonate concretion in OM preservation and highlights their great potential as palaeoenvironmental recorders
Palaeobiology of red and white blood cell-like structures, collagen and cholesterol in an ichthyosaur bone
© 2017 The Author(s). Carbonate concretions are known to contain well-preserved fossils and soft tissues. Recently, biomolecules (e.g. cholesterol) and molecular fossils (biomarkers) were also discovered in a 380 million-year-old concretion, revealing their importance in exceptional preservation of biosignatures. Here, we used a range of microanalytical techniques, biomarkers and compound specific isotope analyses to report the presence of red and white blood cell-like structures as well as platelet-like structures, collagen and cholesterol in an ichthyosaur bone encapsulated in a carbonate concretion from the Early Jurassic (~182.7 Ma). The red blood cell-like structures are four to five times smaller than those identified in modern organisms. Transmission electron microscopy (TEM) analysis revealed that the red blood cell-like structures are organic in composition. We propose that the small size of the blood cell-like structures results from an evolutionary adaptation to the prolonged low oxygen atmospheric levels prevailing during the 70 Ma when ichthyosaurs thrived. The d 13 C of the ichthyosaur bone cholesterol indicates that it largely derives from a higher level in the food chain and is consistent with a fish and cephalopod diet. The combined findings above demonstrate that carbonate concretions create isolated environments that promote exceptional preservation of fragile tissues and biomolecules
Episodic sedimentation on a peri-Tethyan ridge through the MiddleâLate Jurassic transition (VillĂĄny Mountains, southern Hungary)
The VillaÂŽny area, as a central part of the Tisza
microcontinent/terrane along the European margin of
Tethys, was characterized by intense subsidence in the
Early and Middle Triassic, followed by a long interruption
of subsidence in the Late Triassic to Middle Jurassic.
During the MiddleâLate Jurassic transition, marine sedimentation
started with three distinct sedimentary episodes
dated as Late Bathonian, Early Callovian, and MiddleâLate
Callovian, respectively. The succession is terminated by a
thick limestone of Middle Oxfordian age. The sedimentary
features, microfacies, and macroinvertebrate associations
of these four stratigraphic units are documented and illustrated.
The Middle to Late Jurassic sedimentary episodes of
the VillaÂŽny succession record an interplay of local and
global factors and paleogeographical changes. At the
beginning, local tectonic movements governed the main
features of sedimentation, though the role of eustasy was
also essential. From the mid-Callovian onwards, global
climatic, biotic, and paleoceanographical changes controlled
the nature and formation of the local carbonate
sediments. The Callovian stromatolites are attributed to the
activity of sulphate-reducing bacteria in a deep sublittoral,
current-swept environment. Upwelling of eutrophic Tethyan
waters is recorded by the prevalence of the Bositra
filament microfacies in the Callovian. The long submarine
hiatus at around the CallovianâOxfordian transition mirrors
a serious restriction of the carbonate budget, due to sudden
cooling and a change in the oceanic current system
(opening of a circumglobal Tethyan Passage), and to a
higher amount of dissolved CO2. In the Middle Oxfordian,
the carbonate production considerably increased in accordance
with the sudden global warming