Interplay between the bacterial protein deacetylase CobB and the second messenger c-di-GMP.

As a ubiquitous bacterial secondary messenger, c-di-GMP plays key regulatory roles in processes such as bacterial motility and transcription regulation. CobB is the Sir2 family protein deacetylase that controls energy metabolism, chemotaxis, and DNA supercoiling in many bacteria. Using an Escherichia coli proteome microarray, we found that c-di-GMP strongly binds to CobB. Further, protein deacetylation assays showed that c-di-GMP inhibits the activity of CobB and thereby modulates the biogenesis of acetyl-CoA. Interestingly, we also found that one of the key enzymes directly involved in c-di-GMP production, DgcZ, is a substrate of CobB. Deacetylation of DgcZ by CobB enhances its activity and thus the production of c-di-GMP. Our work establishes a novel negative feedback loop linking c-di-GMP biogenesis and CobB-mediated protein deacetylation.

Switchable multi-functional broadband polarization converter in terahertz band.

In this work, we propose a multi-functional broadband terahertz polarization converter based on graphene-VO2 hybrid metamaterial, which can switch between transmissive linear-to-linear conversion and reflective linear-to-circular conversion. The function of the metamaterial can be controlled by both the temperature and the Fermi energy of the graphene. At 298K, the metamaterial converts the y-polarized wave into x-polarized wave in 0.39-1.22THz. In the meanwhile, changing the Fermi energy of graphene, the converted polarization angle can be tuned from 90° to 45°. Increasing the temperature to 358K, the incident linearly polarized wave is reflected into circularly polarized wave. On this condition, tuning the Fermi energy, the metamaterial can separately convert the linear polarization wave into left-circularly polarized wave in 1.57-2.74THz and right-circularly polarized wave in 1.13-1.59THz. Such a switchable multi-functional broadband polarization converter may achieve potential applications in compact terahertz devices and integrated terahertz circuits.

Function switchable broadband wave plate based on the Au-VO2 hybrid metasurface.

In recent years, the integration of active materials into a metasurface to achieve tunable devices has attracted much attention. Here, we design an Au-VO2 hybrid metasurface, which can switch between quarter-wave plate and half-wave plate due to the phase transition of VO2. At 298 K, the proposed structure acts as a quarter-wave plate in the 0.87-1.2 THz band, achieving the mutual conversion between linear polarization and circular polarization. Raising the temperature to 358 K, it works as a broadband half-wave plate in the range of 0.65-1.45 THz, with the reflective chirality preservation of circular polarization and the cross-polarization conversion of linear polarization. In the above cases, the response efficiencies are both above 90%. The switchable multifunction results from the tunable geometric phase of the metasurface, where the elaborately designed Au and VO2 blocks separately bring the phase of π/2. Furthermore, the electric field and current density distributions are employed to explain the physical mechanisms leading to the different functions. Such an active broadband metasurface is expected to find applications in tunable and multifunction devices manipulating the polarization and phase of terahertz waves.

Conserved TCP domain of Sas-4/CPAP is essential for pericentriolar material tethering during centrosome biogenesis.

Pericentriolar material (PCM) recruitment to centrioles forms a key step in centrosome biogenesis. Deregulation of this process leads to centrosome aberrations causing disorders, one of which is autosomal recessive primary microcephaly (MCPH), a neurodevelopmental disorder where brain size is reduced. During PCM recruitment, the conserved centrosomal protein Sas-4/CPAP/MCPH6, known to play a role in centriole formation, acts as a scaffold for cytoplasmic PCM complexes to bind and then tethers them to centrioles to form functional centrosomes. To understand Sas-4's tethering role, we determined the crystal structure of its T complex protein 10 (TCP) domain displaying a solvent-exposed single-layer of ß-sheets fold. This unique feature of the TCP domain suggests that it could provide an "extended surface-like" platform to tether the Sas-4-PCM scaffold to a centriole. Functional studies in Drosophila, human cells, and human induced pluripotent stem cell-derived neural progenitor cells were used to test this hypothesis, where point mutations within the 9-10th ß-strands (ß9-10 mutants including a MCPH-associated mutation) perturbed PCM tethering while allowing Sas-4/CPAP to scaffold cytoplasmic PCM complexes. Specifically, the Sas-4 ß9-10 mutants displayed perturbed interactions with Ana2, a centrosome duplication factor, and Bld-10, a centriole microtubule-binding protein, suggesting a role for the ß9-10 surface in mediating protein-protein interactions for efficient Sas-4-PCM scaffold centriole tethering. Hence, we provide possible insights into how centrosomal protein defects result in human MCPH and how Sas-4 proteins act as a vehicle to tether PCM complexes to centrioles independent of its well-known role in centriole duplication.

Molecular basis for hierarchical histone de-ß-hydroxybutyrylation by SIRT3.

Chemical modifications on histones constitute a key mechanism for gene regulation in chromatin context. Recently, histone lysine ß-hydroxybutyrylation (Kbhb) was identified as a new form of histone acylation that connects starvation-responsive metabolism to epigenetic regulation. Sirtuins are a family of NAD+-dependent deacetylases. Through systematic profiling studies, we show that human SIRT3 displays class-selective histone de-ß-hydroxybutyrylase activities with preference for H3 K4, K9, K18, K23, K27, and H4K16, but not for H4 K5, K8, K12, which distinguishes it from the Zn-dependent HDACs. Structural studies revealed a hydrogen bond-lined hydrophobic pocket favored for the S-form Kbhb recognition and catalysis. ß-backbone but not side chain-mediated interactions around Kbhb dominate sequence motif recognition, explaining the broad site-specificity of SIRT3. The observed class-selectivity of SIRT3 is due to an entropically unfavorable barrier associated with the glycine-flanking motif that the histone Kbhb resides in. Collectively, we reveal the molecular basis for class-selective histone de-ß-hydroxybutyrylation by SIRT3, shedding lights on the function of sirtuins in Kbhb biology through hierarchical deacylation.

Beyond histone acetylation-writing and erasing histone acylations.

Histone post-translational modifications are crucial epigenetic mechanisms regulating a variety of biological events. Besides histone lysine acetylation, a repertoire of acylation types have been identified, including formylation, propionylation, butyrylation, crotonylation, 2-hydroxyisobutyrylation, ß-hydroxybutyrylation, succinylation, malonylation, glutarylation and benzoylation. From a structural perspective, here we summarize the writers and erasers of histone acylations and explain the molecular basis of these enzymes catalyzing non-acetyl histone acylations with a focus on histone crotonylation and ß-hydroxybutyrylation. Histone acylation readout, non-histone acylations and metabolic regulation are also discussed in this review.