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Truncated version of adenylyl cyclase 3 acts as a cold-induced rheostat during long-term brown adipose tissue activation.

The molecular role of ciliary Polycystin-2 (PC2) in cyst formation and polycystic kidney disease (ADKPD) is unclear. Here, the authors identify a PC2 mutant lacking ciliary localisation but with active Ca2+ channel function in mice, that is sufficient to generate an ADPKD phenotype.

Fibrocystin/Polyductin (FPC) is a large ciliary membrane protein encoded by PKHD1 which, when mutated, causes ARPKD. Here, the authors show that FPC suppresses cyst development in the kidney of mouse models through the release and mitochondrial translocation of its C terminal product.

Auxilliary Activity Family 5 (AA5) comprises mononuclear copper radical oxidases with catalytic diversity that is not well characterised. Here, structural, phylogenetic and biochemical analyses advance our understanding of the potential biological and biotechnology functions of these proteins.

Endolysosomal proteolytric cleavage is shown to be required for TLR9 activation by CpG

Adaptive immunity depends on cellular chaperone and quality control systems that are decisive for an effective presentation of foreign antigens via MHC I molecules. Here, the authors present the structure of a key chaperone-MHC I complex.

Kucharska, Ivanochko and Hailemariam and colleagues solved cryo-EM structures of Pfs48/45, needed for Plasmodium falciparum development, with potent antibodies. The work revealed conformational epitopes, with implications for design of therapies against malaria.

Virus triggered lipophagy is important for flaviviral assembly and coordinated by Aup1 and the ubiquitin conjugating enzyme E2. Here, Lan et al further characterise the interplay between these proteins and how they function to modulate selective autophagy and viral replication.

IgG molecules are glycosylated at a conserved asparagine residue of their constant region, and this modification is essential for the effector functions of their soluble form, such as complement activation and binding to Fcɣ receptors. Here authors show that in a model B-cell line, neither the expression nor the function of the membrane-bound form of IgG depend on glycosylation.

Stabilized, native-like trimers of the HIV envelope protein, such as SOSIP trimers, are potential antigens for an HIV vaccine. Here, the authors generate a SOSIP trimer based on the consensus sequence of group M isolates, determine its structure and exposure of common epitopes, and show immunogenicity in rabbits and non-human primates.

A hyper-stable de novo protein mimic of interleukin-2 computationally designed to not interact with a regulatory T-cell specific receptor subunit has improved therapeutic activity in mouse models of melanoma and colon cancer.

The X-ray structure of the hexameric complex of interferon-γ bound to its receptors is solved at 3.25 Å resolution, providing a basis for engineering variants of interferon-γ that enable decoupling of its immunomodulatory functions.

The role of viral Fc-gamma receptors in rhesus cytomegalovirus (RhCMV) infection is unclear. Here, the authors characterized RhCMV vFcγRs and report that their deletion did not affect virus replication, tropism or superinfection in rhesus macaques but increased susceptibility of the virus to antibody control.

Elevated serum urate levels are a risk factor for gout. Here, Tin et al. perform whole-exome sequencing in 19,517 individuals and detect low-frequency genetic variants in urate transporter genes, SLC22A12 and SLC2A9, associated with serum urate levels and confirm their damaging nature in vitro and in silico.

Here, Dirk Lefeber and colleagues identify functional mutations in ATP6AP1 encoding Ac45. The authors show that Ac45 is the functional ortholog of yeast V-ATPase assembly factor Voa1 and provide evidence for tissue-specific Ac45 processing, associated with the clinical phenotype of immunodeficiency, hepatopathy, and neurocognitive abnormalities.

POGLUT1 is a protein-O-glucosyltransferase that transfers glucose and xylose to the EGF-like domains of Notch and other signaling receptors. Here the authors report the structure of human POGLUT1 in complexes with 3 different EGF-like domains and donor substrates and shed light on the enzyme’s substrate specificity and catalytic mechanism

Some broadly neutralizing antibodies to HIV-1 recognize glycan-dependent epitopes on gp120. Now X-ray crystallography and EM approaches, along with functional analyses, reveal how one particular antibody (PGT135) recognizes three glycan groups and can accommodate their conformational and chemical diversity.

CMTM6 and CMTM4 bind to and stabilize the inhibitory receptor PD-L1 and regulate PD-L1 levels at the surface of human tumour and immune cells.

The successful transport of a trapped proton cloud from the antimatter factory of CERN using a transportable, superconducting, autonomous and open Penning-trap system that can distribute antiprotons into other experiments is reported.

Christoph Klein and colleagues identify homozygous mutations in the JAGN1 gene in families and individuals with severe congenital neutropenia. They show that JAGN1 is necessary for the differentiation and survival of neutrophil granulocytes.

Interstitial Lung Disease (ILD)-associated mutations in surfactant protein C (SP-C) render the protein prone to aggregation. Here, the authors reveal their impact on protein maturation, provide insights into recognition of aggregation prone regions by chaperones, and address the autosomal dominant nature of ILD mutants.

The respiratory syncytial virus (RSV) F glycoprotein forms a trimeric complex and mediates viral entry. Using structures of RSV F in complex with antibodies, Gilman et al. here show a breathing motion of the prefusion conformation of F, resulting in transient opening of the trimeric complex in solution and on the cell surface.

A cryo-electron microscopy structure of β-arrestin 1 in complex with the M2 muscarinic receptor reconstituted in lipid nanodiscs is reported.

A survey of SARS-CoV-2 RBD antibodies identifies those with activity against diverse SARS-CoV-2 variants and SARS-related coronaviruses, highlighting epitopes and features to prioritize in antibody and vaccine development.

The human monoclonal antibody S2X259 cross-reacts with spike proteins from all clades of sarbecovirus, and provides prophylactic and therapeutic protection in vivo against parental SARS-CoV-2 and emerging variants of concern.

Insights from structural biology lead to the development of mini-Ins—a human des-octapeptide insulin analog that is monomeric and has receptor binding affinity and in vitro and in vivo activities comparable to those of human insulin.

Two nanobodies that bind SARS-CoV-2 spike RBD are shown to block interaction with receptor ACE2 and thus neutralize the virus, and have an additive effect with antibody CR3022.