The universally conserved enzyme CTP synthase (CTPS) forms filaments in bacteria and eukaryotes. In bacteria polymerization inhibits CTPS activity and is required for nucleotide homeostasis. Here we show that human CTPS polymerization increases catalytic activity. The cryoEM structures of bacterial and human CTPS filaments differ dramatically in overall architecture and in the conformation of the CTPS protomer, explaining the divergent consequences of polymerization on activity. The filament structure of human CTPS is the first full-length structure of the human enzyme and reveals a novel active conformation. The filament structures elucidate allosteric mechanisms of assembly and regulation that rely on a conserved conformational equilibrium. This may provide a mechanism for increasing human CTPS activity in response to metabolic state, and challenges the assumption that metabolic filaments are generally storage forms of inactivated enzymes. Allosteric regulation of CTPS polymerization by ligands likely represents a fundamental mechanism underlying assembly of other metabolic filaments.

This paper presents a comparison of popular period finding algorithms applied to the light curves of variable stars from the Catalina Real-time Transient Survey (CRTS), MACHO and ASAS data sets. We analyze the accuracy of the methods against magnitude, sampling rates, quoted period, quality measures (signal-to-noise and number of observations), variability, and object classes. We find that measure of dispersion-based techniques -analysis-of-variance with harmonics and conditional entropy -consistently give the best results but there are clear dependencies on object class and light curve quality. Period aliasing and identifying a period harmonic also remain significant issues. We consider the performance of the algorithms and show that a new conditional entropy-based algorithm is the most optimal in terms of completeness and speed. We also consider a simple ensemble approach and find that it performs no better than individual algorithms.

Summary Numerous broadly neutralizing antibodies (bnAbs) have been identified that target the glycans of the HIV-1 envelope spike. Neutralization breadth is notable given that glycan processing can be substantially influenced by the presence or absence of neighboring glycans. Here, using a stabilized recombinant envelope trimer, we investigate the degree to which mutations in the glycan network surrounding an epitope impact the fine glycan processing of antibody targets. Using cryo-electron microscopy and site-specific glycan analysis, we reveal the importance of glycans in the formation of the 2G12 bnAb epitope and show that the epitope is only subtly impacted by variations in the glycan network. In contrast, we show that the PG9 and PG16 glycan-based epitopes at the trimer apex are dependent on the presence of the highly conserved surrounding glycans. Glycan networks underpin the conservation of bnAb epitopes and are an important parameter in immunogen design.

1Numerous broadly neutralizing antibodies (bnAbs) have been identified that target the 2 glycans of the HIV-1 envelope spike. Neutralization breadth is notable given that glycan 3 processing can be substantially influenced by the presence or absence of neighboring glycans. 4Here, using a stabilized recombinant envelope trimer, we investigate the degree to which 5 mutations in the glycan network surrounding an epitope impact the fine glycan processing of 6 antibody targets. Using cryo-electron microscopy and site-specific glycan analysis, we reveal 7 the hierarchy of importance of glycans in the formation of the 2G12 bnAb epitope, and show 8 that the epitope is only subtly impacted by variations in the glycan network. In contrast, we 9show that the PG9 and PG16 glycan-based epitopes at the trimer apex are dependent on the 10