A new KSRP-binding compound suppresses distant metastasis of colorectal cancer by targeting the oncogenic KITENIN complex.

Background: Distant metastasis is the major cause of death in patients with colorectal cancer (CRC). Previously, we identified KITENIN as a metastasis-enhancing gene and suggested that the oncogenic KITENIN complex is involved in metastatic dissemination of KITENIN-overexpressing CRC cells. Here, we attempted to find substances targeting the KITENIN complex and test their ability to suppress distant metastasis of CRC.

COVID-19 serological survey using micro blood sampling.

During August 2020, we carried out a serological survey among students and employees at the Okinawa Institute of Science and Technology Graduate University (OIST), Japan, testing for the presence of antibodies against SARS-CoV-2, the causative agent of COVID-19. We used a FDA-authorized 2-step ELISA protocol in combination with at-home self-collection of blood samples using a custom low-cost finger prick-based capillary blood collection kit. Although our survey did not find any COVID-19 seropositive individuals among the OIST cohort, it reliably detected all positive control samples obtained from a local hospital and excluded all negatives controls.

Biomimetic Crack Sensors Using Electrohydrodynamic Technology.

This paper proposes a new mechanism for detecting microscopic damage of structures based on imitating the sensory organs of spiders. Therefore, it is essential to manufacture sensors that can react sensitively to the micro deformations of structures. Numerous cracks were intentionally generated to improve the sensitivity of the proposed sensor, and an increase in the gap of the crack was observed by scanning electron microscopy (SEM) observation.

MYO1D binds with kinase domain of the EGFR family to anchor them to plasma membrane before their activation and contributes carcinogenesis.

The cell surface receptor tyrosine kinase (RTK) exists in a dynamic state, however, it remains unknown how single membrane-spanning RTK proteins are retained in the plasma membrane before their activation. This study was undertaken to investigate how RTK proteins are anchored in the plasma membrane before they bind with their respective extracellular ligands for activation through protein-protein interaction, co-localization, and functional phenotype studies. Here we show that unconventional myosin-I MYO1D functions to hold members of the EGFR family (except ErbB3) at the plasma membrane.

Structures of three ependymin-related proteins suggest their function as a hydrophobic molecule binder.

Ependymin was first discovered as a predominant protein in brain extracellular fluid in fish and was suggested to be involved in functions mostly related to learning and memory. Orthologous proteins to ependymin called ependymin-related proteins (EPDRs) have been found to exist in various tissues from sea urchins to humans, yet their functional role remains to be revealed. In this study, the structures of EPDR1 from frog, mouse and human were determined and analyzed.

The carboxy-terminal region of the TBC1D4 (AS160) RabGAP mediates protein homodimerization.

TBC1D4 (also known as AS160) is a Rab·GTPase-activating protein (RabGAP) which functions in insulin signaling. TBC1D4 is critical for translocation of glucose transporter 4 (GLUT4), from an inactive, intracellular, vesicle-bound site to the plasma membrane, where it promotes glucose entry into cells. The TBC1D4 protein is structurally subdivided into two N-terminal phosphotyrosine-binding (PTB) domains, a C-terminal catalytic RabGAP domain, and a disordered segment in between containing potential Akt phosphorylation sites.

In Streptomyces coelicolor SigR, methionine at the -35 element interacting region 4 confers the -31'-adenine base selectivity.

In Gram-positive Streptomyces coelicolor A3(2), SigR (Sc σ(R)) of the group IV ECF sigma factor singly activates expression of more than 30 oxidation responsive genes. Of the two promoter-binding domains--individually called region 2 and region 4 - within Sc σ(R), we hereby report a 2.6 Å resolution structure of the -35 element interacting carboxyl-terminal region 4 (Sc σ(R)4).

FcγRIIB Gene Polymorphisms Are Associated with Disease Risk and Clinical Manifestations of Systemic Lupus Erythematosus in Koreans.

Systemic lupus erythematosus (SLE) is chronic autoimmune disease with various autoantibodies, which are involved in tissue damage. Fc gamma receptors (FcγRs) bind the constant region of the immunoglobulin G and transmit stimulatory or inhibitory signal to immune cells. The FcγR genes map to 1q23, a susceptible locus for SLE.

Overproduction, crystallization and preliminary X-ray crystallographic analysis of Escherichia coli tRNA N6-threonylcarbamoyladenosine dehydratase.

Escherichia coli tRNA N6-threonylcarbamoyladenosine dehydratase (TcdA), previously called CsdL or YgdL, was overproduced and purified from E. coli and crystallized using polyethylene glycol 3350 as a crystallizing agent. X-ray diffraction data were collected to 2.

Crystallization and preliminary X-ray crystallographic analysis of carboxyl-terminal region 4 of SigR from Streptomyces coelicolor A3(2).

Full-length SigR from Streptomyces coelicolor A3(2) was overexpressed in Escherichia coli, purified and submitted to crystallization trials using either polyethylene glycol 3350 or 4000 as a precipitant. X-ray diffraction data were collected to 2.60 Å resolution under cryoconditions using synchrotron X-rays.

Discovery and the structural basis of a novel p21-activated kinase 4 inhibitor.

Functional versatility and elevated expression in cancers have endowed p21-activated kinase 4 (PAK4) as one of the first-in-class anti-cancer drug target. In this study, a novel PAK4 inhibitor, KY-04031 (N(2)-(2-(1H-indol-3-yl)ethyl)-N(4)-(1H-indazol-5-yl)-6-methoxy-1,3,5-triazine-2,4-diamine), was discovered using a high-throughput screening. Analysis of the complex crystal structure illustrated that both indole and indazole of KY-04031 are responsible for PAK4 hinge interaction.

RNA editing in RHOQ promotes invasion potential in colorectal cancer.

RNA editing can increase RNA sequence variation without altering the DNA sequence. By comparing whole-genome and transcriptome sequence data of a rectal cancer, we found novel tumor-associated increase of RNA editing in ras homologue family member Q (RHOQ) transcripts. The adenosine-to-inosine (A-to-I) editing results in substitution of asparagine with serine at residue 136.

Affinity between TBC1D4 (AS160) phosphotyrosine-binding domain and insulin-regulated aminopeptidase cytoplasmic domain measured by isothermal titration calorimetry.

Uptake of circulating glucose into the cells happens via the insulin- mediated signalling pathway, which translocates the glucose transporter 4 (GLUT4) vesicles from the intracellular compartment to the plasma membrane. RabㆍGTPases are involved in this vesicle trafficking, where RabㆍGTPase-activating proteins (RabGAP) enhance the GTP to GDP hydrolysis. TBC1D4 (AS160) and TBC1D1 are functional RabGAPs in the adipocytes and the skeletonal myocytes, respectively.

Crystallization and preliminary X-ray crystallographic analysis of Thermotoga maritima CheA P3-P4-P5 domains in complex with CheW.

The CheA-CheW complex plays a key role in bacterial chemotaxis signal transduction by initiating phosphotransfer to response regulators via coupling to the chemoreceptors. CheA (P3-P4-P5 domains) and CheW from Thermotoga maritima were overexpressed in Escherichia coli and crystallized as a complex at 298 K using ammonium dihydrogen phosphate as a precipitant. X-ray diffraction data were collected to ~8 Å resolution at 100 K using synchrotron radiation.

Crystallization and preliminary X-ray crystallographic analysis of Escherichia coli CheA P3 dimerization domain.

The chemotaxis histidine kinase CheA assembles into a dimer in which the P3 dimerization domain forms a four-helix bundle by the parallel association of two α-helical hairpins from each subunit. Ligand occupancy of the chemoreceptor regulates signal transduction by controlling the autophosphorylation activity of CheA. Autophosphorylation of CheA occurs in trans, i.