Czech National Centre of the European Research Infrastructure Consortium INSTRUCT ERIC

Micro-CT images of P0 pups with control and low iron diet, containing 178.58 mg iron/kg or 5.16 mg iron/kg, respectively. The kidney (red), interscapular brown adipose tissue (IBAT) (yellow), liver (green), and adrenal glands (orange) are segmented using 3D Visualization software and superimposed onto the pups.

Julian Petersen and Igor Adamyeko Research Group

Significance

In this study, we use comparative genomics to uncover a gene with uncharacterized function (1700011H14Rik/C14orf105/CCDC198), which we hereby name FAME (Factor Associated with Metabolism and Energy). We observe that FAME shows an unusually high evolutionary divergence in birds and mammals. Through the comparison of single nucleotide polymorphisms, we identify gene flow of FAME from Neandertals into modern humans. We conduct knockout experiments on animals and observe altered body weight and decreased energy expenditure in Fame knockout animals, corresponding to genome-wide association studies linking FAME with higher body mass index in humans. Gene expression and subcellular localization analyses reveal that FAME is a membrane-bound protein enriched in the kidneys. Although the gene knockout results in structurally normal kidneys, we detect higher albumin in urine and lowered ferritin in the blood. Through experimental validation, we confirm interactions between FAME and ferritin and show co-localization in vesicular and plasma membranes.

Petersen, J., Englmaier, L., Artemov, A.V. et al. A previously uncharacterized Factor Associated with Metabolism and Energy (FAME/C14orf105/CCDC198/1700011H14Rik) is related to evolutionary adaptation, energy balance, and kidney physiology.

Nat Commun. 14, 3092 (2023). https://doi.org/10.1038/s41467-023-38663-7

a, The view of the C₂S₂ supercomplex from the lumenal side with indicated subunits of light-harvesting antenna, Lhcb5, Lhcb8 and the S-LHCII trimer, bound to the dimeric core complex. b, The side view of the C₂S₂ supercomplex along the membrane plane. c, Assigned subunits of the core complex.

Roman Kouřil Research Group

Significance

The heart of oxygenic photosynthesis is the water-splitting photosystem II (PSII), which forms supercomplexes with a variable amount of peripheral trimeric light-harvesting complexes (LHCII). Our knowledge of the structure of green plant PSII supercomplex is based on findings obtained from several representatives of green algae and flowering plants; however, data from a non-flowering plant are currently missing. Here we report a cryo-electron microscopy structure of PSII supercomplex from spruce, a representative of non-flowering land plants, at 2.8 Å resolution. Compared with flowering plants, PSII supercomplex in spruce contains an additional Ycf12 subunit, Lhcb4 protein is replaced by Lhcb8, and trimeric LHCII is present as a homotrimer of Lhcb1. Unexpectedly, we have found α-tocopherol (α-Toc)/α-tocopherolquinone (α-TQ) at the boundary between the LHCII trimer and the inner antenna CP43. The molecule of α-Toc/α-TQ is located close to chlorophyll a614 of one of the Lhcb1 proteins and its chromanol/quinone head is exposed to the thylakoid lumen. The position of α-Toc in PSII supercomplex makes it an ideal candidate for the sensor of excessive light, as α-Toc can be oxidized to α-TQ by high-light-induced singlet oxygen at low lumenal pH. The molecule of α-TQ appears to shift slightly into the PSII supercomplex, which could trigger important structure–functional modifications in PSII supercomplex. Inspection of the previously reported cryo-electron microscopy maps of PSII supercomplexes indicates that α-Toc/α-TQ can be present at the same site also in PSII supercomplexes from flowering plants, but its identification in the previous studies has been hindered by insufficient resolution.

Opatíková, M., Semchonok, D.A., Kopečný, D. et al. Cryo-EM structure of a plant photosystem II supercomplex with light-harvesting protein Lhcb8 and α-tocopherol.

Nat. Plants 9, 1359–1369 (2023). https://doi.org/10.1038/s41477-023-01483-0

The central ring shows a superimposition of the binding sites on the SSU (gray) of the antibiotics tetracycline (blue), spectinomycin (yellow), hygromycin B (pink), kasugamycin (red), apramycin (green), gentamicin (cyan) and streptomycin (orange), which is surrounded by insets highlighting the interactions between the drug and the 16S rRNA (gray), waters (red spheres with gray transparent density), magnesium ions (green spheres), putative K⁺ ions (purple sphere with transparent gray density) and uS12 (orange). Potential hydrogen bonds are indicated as dashed lines, colored orange for direct interaction between the drug and the small subunit, cyan for water-mediated interactions, green for Mg²⁺ ion coordination and purple for K⁺ coordination.

Daniel Wilson Research Group

Significance

The ribosome is a major target for clinically used antibiotics, but multidrug resistant pathogenic bacteria are making our current arsenal of antimicrobials obsolete. Here we present cryo-electron-microscopy structures of 17 distinct compounds from six different antibiotic classes bound to the bacterial ribosome at resolutions ranging from 1.6 to 2.2 Å. The improved resolution enables a precise description of antibiotic–ribosome interactions, encompassing solvent networks that mediate multiple additional interactions between the drugs and their target. Our results reveal a high structural conservation in the binding mode between antibiotics with the same scaffold, including ordered water molecules. Water molecules are visualized within the antibiotic binding sites that are preordered, become ordered in the presence of the drug and that are physically displaced on drug binding. Insight into RNA–ligand interactions will facilitate development of new antimicrobial agents, as well as other RNA-targeting therapies.

Paternoga, H., Crowe-McAuliffe, C., Bock, L.V. et al. Structural conservation of antibiotic interaction with ribosomes.

Nat Struct Mol Biol (2023). https://doi.org/10.1038/s41594-023-01047-y