growth-electrostaticchemical-properties-metallaalo3srtio3

Growth and Electrostatic/chemical Properties of Metal/LaAlO<sub>3</sub>/SrTiO<sub>3</sub> Heterostructures

The quasi 2D electron system (q2DES) that forms at the interface between LaAlO3 (LAO) and SrTiO3 (STO) has attracted much attention from the oxide ...

Université Paris-Saclay

In the Drosophila circadian oscillator, the CLOCK/CYCLE complex activates transcription of period (per) and timeless (tim) in the evening. PER and TIM proteins then repress CLOCK (CLK) activity during the night. The pace of the oscillator depends upon post-translational regulation that affects both positive and negative components of the transcriptional loop. CLK protein is highly phosphorylated and inactive in the morning, whereas hypophosphorylated active forms are present in the evening. How this critical dephosphorylation step is mediated is unclear. We show here that two components of the STRIPAK complex, the CKA regulatory subunit of the PP2A phosphatase and its interacting protein STRIP, promote CLK dephosphorylation during the daytime. In contrast, the WDB regulatory PP2A subunit stabilizes CLK without affecting its phosphorylation state. Inhibition of the PP2A catalytic subunit and CKA downregulation affect daytime CLK similarly, suggesting that STRIPAK complexes are the main PP2A players in producing transcriptionally active hypophosphorylated CLK.

Daytime CLOCK Dephosphorylation Is Controlled by STRIPAK Complexes in Drosophila.

Understanding the structural basis of actin cytoskeleton remodeling requires stabilization of actin monomers, oligomers, and filaments in complex with partner proteins, using various biochemical strategies. Here, we report a dramatic destabilization of the dynamic interaction with a model β-thymosin/WH2 domain induced by mutations in actin. This result underlines that mutant actins should be used with prudence to characterize interactions with intrinsically disordered partners as destabilization of dynamic interactions, although identifiable by NMR, may be invisible to other structural techniques. It also highlights how both β-thymosin/WH2 domains and actin tune local structure and dynamics in regulatory processes involving intrinsically disordered domains.

Mutations in actin used for structural studies partially disrupt β-thymosin/WH2 domains interaction.

Bacteriophage capsids constitute icosahedral shells of exceptional stability that protect the viral genome. Many capsids display on their surface decoration proteins whose structure and function remain largely unknown. The decoration protein pb10 of phage T5 binds at the centre of the 120 hexamers formed by the major capsid protein. Here we determined the 3D structure of pb10 and investigated its capsid-binding properties using NMR, SAXS, cryoEM and SPR. Pb10 consists of an α-helical capsid-binding domain and an Ig-like domain exposed to the solvent. It binds to the T5 capsid with a remarkably high affinity and its binding kinetics is characterized by a very slow dissociation rate. We propose that the conformational exchange events observed in the capsid-binding domain enable rearrangements upon binding that contribute to the quasi-irreversibility of the pb10-capsid interaction. Moreover we show that pb10 binding is a highly cooperative process, which favours immediate rebinding of newly dissociated pb10 to the 120 hexamers of the capsid protein. In extreme conditions, pb10 protects the phage from releasing its genome. We conclude that pb10 may function to reinforce the capsid thus favouring phage survival in harsh environments.

High affinity anchoring of the decoration protein pb10 onto the bacteriophage T5 capsid.

The quasi 2D electron system (q2DES) that forms at the interface between LaAlO3 and SrTiO3 has attracted much attention from the oxide electronics community. One of its hallmark features is the existence of a critical LaAlO3 thickness of 4 unit-cells (uc) for interfacial conductivity to emerge. In this paper, the chemical, electronic, and transport properties of LaAlO3 /SrTiO3 samples capped with different metals grown in a system combining pulsed laser deposition, sputtering, and in situ X-ray photoemission spectroscopy are investigated. The results show that for metals with low work function a q2DES forms at 1-2 uc of LaAlO3 and is accompanied by a partial oxidation of the metal, a phenomenon that affects the q2DES properties and triggers the formation of defects. In contrast, for noble metals, the critical thickness is increased above 4 uc. The results are discussed in terms of a hybrid mechanism that incorporates electrostatic and chemical effects.

Tuning Up or Down the Critical Thickness in LaAlO3 /SrTiO3 through In Situ Deposition of Metal Overlayers.

Quantitative real-time RT-PCR (RT-qPCR) has become the method of choice for mRNA quantification, but requires an accurate normalization based on the use of reference genes showing invariant expression across various pathological conditions. Only few data exist on appropriate reference genes for the human heart. The objective of this study was to determine a set of suitable reference genes in human atrial and ventricular tissues, from right and left cavities in control and in cardiac diseases.

Identification of optimal reference genes for transcriptomic analyses in normal and diseased human heart.

Unexpected peptide deformylase (PDF) genes were recently retrieved in numerous marine phage genomes. While various hypotheses dealing with the occurrence of these intriguing sequences have been made, no further characterization and functional studies have been described thus far. In this study, we characterize the bacteriophage Vp16 PDF enzyme, as representative member of the newly identified C-terminally truncated viral PDFs. We show here that conditions classically used for bacterial PDFs lead to an enzyme exhibiting weak activity. Nonetheless, our integrated biophysical and biochemical approaches reveal specific effects of pH and metals on Vp16 PDF stability and activity. A novel purification protocol taking in account these data allowed strong improvement of Vp16 PDF specific activity to values similar to those of bacterial PDFs. We next show that Vp16 PDF is as sensitive to the natural inhibitor compound of PDFs, actinonin, as bacterial PDFs. Comparison of the 3D structures of Vp16 and E. coli PDFs bound to actinonin also reveals that both PDFs display identical substrate binding mode. We conclude that bacteriophage Vp16 PDF protein has functional peptide deformylase activity and we suggest that encoded phage PDFs might be important for viral fitness.

Article	Year
Daytime CLOCK Dephosphorylation Is Controlled by STRIPAK Complexes in Drosophila. Cell reports\| PubMed ID: 25981041	2015
Mutations in actin used for structural studies partially disrupt β-thymosin/WH2 domains interaction. FEBS letters\| PubMed ID: 27680677	2016
High affinity anchoring of the decoration protein pb10 onto the bacteriophage T5 capsid. Scientific reports\| PubMed ID: 28165000	2017
Tuning Up or Down the Critical Thickness in LaAlO3 /SrTiO3 through In Situ Deposition of Metal Overlayers. Advanced materials (Deerfield Beach, Fla.)\| PubMed ID: 28505388	2017
Identification of optimal reference genes for transcriptomic analyses in normal and diseased human heart. Cardiovascular research\| PubMed ID: 29036603	2018
Peptide deformylases from Vibrio parahaemolyticus phage and bacteria display similar deformylase activity and inhibitor binding clefts. Biochimica et biophysica acta\| PubMed ID: 29101077	2018

Eric Jacquet

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