A redox-active switch in fructosamine-3-kinases expands the regulatory repertoire of the protein kinase superfamily

Aberrant regulation of metabolic kinases by altered redox homeostasis substantially contributes to aging and various diseases, such as diabetes. We found that the catalytic activity of a conserved family of fructosamine-3-kinases (FN3Ks), which are evolutionarily related to eukaryotic protein kinases, is regulated by redox-sensitive cysteine residues in the kinase domain. The crystal structure of the FN3K homolog from Arabidopsis thaliana revealed that it forms an unexpected strand-exchange dimer in which the ATP-binding P-loop and adjoining β strands are swapped between two chains in the dimer. This dimeric configuration is characterized by strained interchain disulfide bonds that stabilize the P-loop in an extended conformation. Mutational analysis and solution studies confirmed that the strained disulfides function as redox “switches” to reversibly regulate the activity and dimerization of FN3K. Human FN3K, which contains an equivalent P-loop Cys, was also redox sensitive, whereas ancestral bacterial FN3K homologs, which lack a P-loop Cys, were not. Furthermore, CRISPR-mediated knockout of FN3K in human liver cancer cells altered the abundance of redox metabolites, including an increase in glutathione. We propose that redox regulation evolved in FN3K homologs in response to changing cellular redox conditions. Our findings provide insights into the origin and evolution of redox regulation in the protein kinase superfamily and may open new avenues for targeting human FN3K in diabetic complications

Volatile and Organic Compositions of Sedimentary Rocks in Yellowknife Bay, Gale crater, Mars

H₂O, CO₂, SO₂, O₂, H₂, H₂S, HCl, chlorinated hydrocarbons, NO and other trace gases were evolved during pyrolysis of two mudstone samples acquired by the Curiosity rover at Yellowknife Bay within Gale crater, Mars. H₂O/OH-bearing phases included 2:1 phyllosilicate(s), bassanite, akaganeite, and amorphous materials. Thermal decomposition of carbonates and combustion of organic materials are candidate sources for the CO₂. Concurrent evolution of O₂ and chlorinated hydrocarbons suggest the presence of oxychlorine phase(s). Sulfides are likely sources for S-bearing species. Higher abundances of chlorinated hydrocarbons in the mudstone compared with Rocknest windblown materials previously analyzed by Curiosity suggest that indigenous martian or meteoritic organic C sources may be preserved in the mudstone; however, the C source for the chlorinated hydrocarbons is not definitively of martian origin

The Petrochemistry of Jake_M: A Martian Mugearite

“Jake_M,” the first rock analyzed by the Alpha Particle X-ray Spectrometer instrument on the Curiosity rover, differs substantially in chemical composition from other known martian igneous rocks: It is alkaline (>15% normative nepheline) and relatively fractionated. Jake_M is compositionally similar to terrestrial mugearites, a rock type typically found at ocean islands and continental rifts. By analogy with these comparable terrestrial rocks, Jake_M could have been produced by extensive fractional crystallization of a primary alkaline or transitional magma at elevated pressure, with or without elevated water contents. The discovery of Jake_M suggests that alkaline magmas may be more abundant on Mars than on Earth and that Curiosity could encounter even more fractionated alkaline rocks (for example, phonolites and trachytes)

Elemental Geochemistry of Sedimentary Rocks at Yellowknife Bay, Gale Crater, Mars

Sedimentary rocks examined by the Curiosity rover at Yellowknife Bay, Mars, were derived from sources that evolved from approximately average Martian crustal composition to one influenced by alkaline basalts. No evidence of chemical weathering is preserved indicating arid, possibly cold, paleoclimates and rapid erosion/deposition. Absence of predicted geochemical variations indicates that magnetite and phyllosilicates formed by diagenesis under low temperature, circum-neutral pH, rock-dominated aqueous conditions. High spatial resolution analyses of diagenetic features, including concretions, raised ridges and fractures, indicate they are composed of iron- and halogen-rich components, magnesium-iron-chlorine-rich components and hydrated calcium-sulfates, respectively. Composition of a cross-cutting dike-like feature is consistent with sedimentary intrusion. Geochemistry of these sedimentary rocks provides further evidence for diverse depositional and diagenetic sedimentary environments during the early history of Mars

A Habitable Fluvio-Lacustrine Environment at Yellowknife Bay, Gale Crater, Mars

The Curiosity rover discovered fine-grained sedimentary rocks, inferred to represent an ancient lake, preserve evidence of an environment that would have been suited to support a Martian biosphere founded on chemolithoautotrophy. This aqueous environment was characterized by neutral pH, low salinity, and variable redox states of both iron and sulfur species. C, H, O, S, N, and P were measured directly as key biogenic elements, and by inference N and P are assumed to have been available. The environment likely had a minimum duration of hundreds to tens of thousands of years. These results highlight the biological viability of fluvial-lacustrine environments in the post-Noachian history of Mars

X-ray Diffraction Results from Mars Science Laboratory: Mineralogy of Rocknest at Gale Crater

The Mars Science Laboratory rover Curiosity scooped samples of soil from the Rocknest aeolian bedform in Gale crater. Analysis of the soil with the Chemistry and Mineralogy (CheMin) x-ray diffraction (XRD) instrument revealed plagioclase (~An57), forsteritic olivine (~Fo62), augite, and pigeonite, with minor K-feldspar, magnetite, quartz, anhydrite, hematite, and ilmenite. The minor phases are present at, or near, detection limits. The soil also contains 27 ± 14 weight percent x-ray amorphous material, likely containing multiple Fe^(3+)- and volatile-bearing phases, including possibly a substance resembling hisingerite. The crystalline component is similar to the normative mineralogy of certain basaltic rocks from Gusev crater on Mars and of martian basaltic meteorites. The amorphous component is similar to that found on Earth in places such as soils on the Mauna Kea volcano, Hawaii

Mineralogy of a Mudstone at Yellowknife Bay, Gale Crater, Mars

Sedimentary rocks at Yellowknife Bay (Gale Crater) on Mars include mudstone sampled by the Curiosity rover. The samples, John Klein and Cumberland, contain detrital basaltic minerals, Ca-sulfates, Fe oxide/hydroxides, Fe-sulfides, amorphous material, and trioctahedral smectites. The John Klein smectite has basal spacing of ~10 Å indicating little interlayer hydration. The Cumberland smectite has basal spacing at ~13.2 Å as well as ~10 Å. The ~13.2 Å spacing suggests a partially chloritized interlayer or interlayer Mg or Ca facilitating H_2O retention. Basaltic minerals in the mudstone are similar to those in nearby eolian deposits. However, the mudstone has far less Fe-forsterite, possibly lost with formation of smectite plus magnetite. Late Noachian/Early Hesperian or younger age indicates that clay mineral formation on Mars extended beyond Noachian time

A redox-active switch in fructosamine-3-kinases expands the regulatory repertoire of the protein kinase superfamily

Aberrant regulation of metabolic kinases by altered redox homeostasis substantially contributes to aging and various diseases, such as diabetes. We found that the catalytic activity of a conserved family of fructosamine-3-kinases (FN3Ks), which are evolutionarily related to eukaryotic protein kinases, is regulated by redox-sensitive cysteine residues in the kinase domain. The crystal structure of the FN3K homolog from Arabidopsis thaliana revealed that it forms an unexpected strand-exchange dimer in which the ATP-binding P-loop and adjoining β strands are swapped between two chains in the dimer. This dimeric configuration is characterized by strained interchain disulfide bonds that stabilize the P-loop in an extended conformation. Mutational analysis and solution studies confirmed that the strained disulfides function as redox "switches" to reversibly regulate the activity and dimerization of FN3K. Human FN3K, which contains an equivalent P-loop Cys, was also redox sensitive, whereas ancestral bacterial FN3K homologs, which lack a P-loop Cys, were not. Furthermore, CRISPR-mediated knockout of FN3K in human liver cancer cells altered the abundance of redox metabolites, including an increase in glutathione. We propose that redox regulation evolved in FN3K homologs in response to changing cellular redox conditions. Our findings provide insights into the origin and evolution of redox regulation in the protein kinase superfamily and may open new avenues for targeting human FN3K in diabetic complications

Low upper limit to methane abundance on Mars

By analogy with Earth, methane in the Martian atmosphere is a potential signature of ongoing or past biological activity. During the past decade, Earth-based telescopic observations reported "plumes" of methane of tens of parts per billion by volume (ppbv), and those from Mars orbit showed localized patches, prompting speculation of sources from subsurface bacteria or nonbiological sources. From in situ measurements made with the Tunable Laser Spectrometer (TLS) on Curiosity using a distinctive spectral pattern specific to methane, we report no detection of atmospheric methane with a measured value of 0.18 +/- 0.67 ppbv corresponding to an upper limit of only 1.3 ppbv (95% confidence level), which reduces the probability of current methanogenic microbial activity on Mars and limits the recent contribution from extraplanetary and geologic sources