ERRγ-DBD undergoes dimerization and conformational rearrangement upon binding to the downstream site of the DR1 element.

The estrogen-related receptor (ERR) family members are reported to bind DNA elements as either monomer or dimer. However, to date, only one solution NMR structure of ERRß in complex with a half-site DNA element has been reported. To better understand the DNA regulation mechanism, we determined the crystal structure of ERRγ-DBD bound to a natural DR1 element in Pla2g12b promoter to 2.2 Å resolution. Combined with biochemical assays, we show that ERRγ acts as a dimer and the C-terminal extension region undergoes conformational rearrangement when binding to the downstream DR1 element. In addition, the T-box region on the dimerization interface exhibits unique main-chain conformation. Thus, our structure presents a novel dimer interface for NR binding on DR1 DNA and provides a molecular basis for understanding the homodimer organization of ERR on DR1 elements.

Privacy preserving IoT-based crowd-sensing network with comparable homomorphic encryption and its application in combating COVID19.

IoT-based crowd-sensing network, which aims to achieve data collection and task allocation to mobile users, become more and more popular in recent years. This data collected by IoT devices may be private and directly transmission of these data maybe incur privacy leakage. With the help of homomorphic encryption (HE), which supports the additive and/or multiplicative operations over the encrypted data, privacy preserving crowd-sensing network is now possible. Until now several such secure data aggregation schemes based on HE have been proposed. In many cases, ciphertext comparison is an important step for further secure data processing. However efficient ciphertext comparison is not supported by most such schemes. In this paper, aiming at enabling ciphertext comparison among multiple users in crowd-sensing network, with Lagrange's interpolation technique we propose comparable homomorphic encryption (CompHE) schemes. We also prove our schemes' security, and the performance analysis show our schemes are practical. We also discuss the applications of our IoT based crowd-sensing network with comparable homomorphic encryption for combatting COVID19, including the first example of privacy preserving close contact determination based on the spatial distance, and the second example of privacy preserving social distance controlling based on the spatial difference of lockdown zones, controlled zones and precautionary zones. From the analysis we see our IoT based crowd-sensing network can be used for contact tracing without worrying about the privacy leakage. Compared with the existing CompHE schemes, our proposals can be collusion resistance or secure in the semi-honest model while the previous schemes cannot achieve this easily. Our schemes only need 4 or 5 modular exponentiation when implementing the most important comparison algorithm, which are better than the existing closely related scheme with advantage of 50% or 37.5%.

Substrate-induced dimerization of elaiophylin glycosyltransferase reveals a novel self-activating form of glycosyltransferase for symmetric glycosylation.

Elaiophylin (Ela), a unique 16-membered symmetric macrodiolide antibiotic, displays broad biological activity. Two rare 2-deoxy-L-fucose moieties at the ends of Ela are critical for its activity. Previously, elaiophylin glycosyltransferase (ElaGT) was identified as the enzyme that is responsible for the symmetric glycosylation of Ela, acting as a potential enzymatic tool for enhancing the diversity and activity of Ela. However, a symmetric catalytic mechanism has never been reported for a glycosyltransferase (GT). To explore the catalytic mechanism, the structure of ElaGT was determined in four forms: the apo form and Ela-bound, thymidine diphosphate-bound and uridine diphosphate-bound forms. In the Ela-bound structure, two ElaGTs form a `face-to-face' C2-symmetric homodimer with a continuous acceptor-binding pocket, allowing a molecule of Ela to shuffle through. Interestingly, this dimer interface resembles that of the activator-dependent GT EryCIII with its activator EryCII. Sequence analysis also indicates that ElaGT belongs to the activator-dependent GT family, but no putative activator has been identified in the Ela gene cluster. It was then found that the ElaGT homodimer may utilize this `face-to-face' arrangement to stabilize the Ela-binding loops on the interface and to simultaneously allosterically regulate the catalytic center. Therefore, these structures present a novel self-activating model for symmetric sugar transfer in the GT family and a new potential regulation site for substrate specificity.

Molecular Basis for PI(3,5)P2 Recognition by SNX11, a Protein Involved in Lysosomal Degradation and Endosome Homeostasis Regulation.

Phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2) is an essential phosphoinositide required for endosome homeostasis and sorting for lysosomal degradation; however, the underlying mechanisms, especially in mammals, remain elusive or unexplored. Here we determined a structure of PI(3,5)P2 bound to Sorting Nexin 11 (SNX11) with an opened PPII-C loop. We also obtained an SNX11 structure with its PPII-C in "closed" form that serves as a potential PI3P-binding model. In addition, our results reveal that SNX11 can interact with the V1D subunit of vacuolar H+-ATPase (V-ATPase), which provides a link between PI(3,5)P2 and human V-ATPase and further evidence for their roles in the endosome homeostasis regulation. Lastly, a new apo-form structure of SNX11, combined with molecular dynamics (MD) studies, indicates that the α5 helix can unfold from the PX domain of SNX11 when targeting the membrane or interacting with its partner. Taken together, these findings identify a novel PI(3,5)P2 effector, which will shed light on the PIs recognizing mechanism and the understanding of the downstream sorting events triggered by different PI binding.