A cryptic phosphate-binding pocket on the SPFH domain of human stomatin that regulates a novel fibril-like self-assembly.

Human stomatin (hSTOM) is a component of the membrane skeleton of erythrocytes that maintains the membrane's shape and stiffness through interconnecting spectrin and actin. hSTOM is a member of the protein family that possesses a single stomatin/prohibitin/flotillin/HflK (SPFH) domain at the center of the molecule. Although SPFH domain proteins are widely distributed from archaea to mammals, the detailed function of the domain remains unclear.

Relevance of Amorphous and Amyloid-Like Aggregates of the p53 Core Domain to Loss of its DNA-Binding Activity.

The anti-oncogenic protein p53 is a transcription factor that prevents tumorigenesis by inducing gene repair proteins or apoptosis under DNA damage. Since the DNA-binding domain of p53 (p53C) is aggregation-prone, the anti-oncogenic function of p53 is often lost in cancer cells. This tendency is rather severe in some tumor-related p53 mutants, such as R175H.

Potential of rescue and reactivation of tumor suppressor p53 for cancer therapy.

The tumor suppressor protein p53, a transcription product of the anti-oncogene , is a critical factor in preventing cellular cancerization and killing cancer cells by inducing apoptosis. As a result, p53 is often referred to as the "guardian of the genome." Almost half of cancers possess genetic mutations in the gene, and most of these mutations result in the malfunction of p53, which promotes aggregation.

A special issue of the Australian society for Biophysics.

On behalf of the Australian Society for Biophysics (ASB) and the Editors of this Special Issue, I would like to express our appreciation to Editor-in-Chief, Damien Hall, for arranging the publication of this Special Issue. The ASB is about five times smaller than our sister the Biophysical Society for Japan (BSJ) and tenfold smaller than the US Biophysical Society (USBS), but our meetings are notable because of the encouragement the Society gives to emerging biophysicists. It can be a terrifying experience for a PhD student to have to face a roomful of professors and senior academics, but invariably they appreciate the experience.

Bex1 is essential for ciliogenesis and harbours biomolecular condensate-forming capacity.

Background: Primary cilia are sensory organelles crucial for organ development. The pivotal structure of the primary cilia is a microtubule that is generated via tubulin polymerization reaction that occurs in the basal body. It remains to be elucidated how molecules with distinct physicochemical properties contribute to the formation of the primary cilia.

Direct inhibition of the first PDZ domain of ZO-1 by glycyrrhizin is a possible mechanism of tight junction opening of Caco-2 cells.

Glycyrrhizin (GL) is known to exhibit a variety of useful pharmacological activities, including anti-inflammation, anti-hepatotoxicity, and enhancement of intestinal drug absorption. GL has been reported to modify the assembly of actin filaments, thereby modulating tight junction (TJ) integrity, but the detailed molecular mechanisms of this remain unclear. In this study, we first found that GL binds to the first PDZ domain of zonula occludens-1 (ZO-1(PDZ1)) through NMR experiments.

Announcing the call for the Special Issue on "The Australian Society for Biophysics (ASB) - 2021 Meeting".

This Commentary describes a call for submissions for the upcoming Special Issue focused on the research topics presented at the Australian Society of Biophysics (ASB) in 2020 and 2021. Submissions from past and present ASB members who could not attend these meetings are also welcome as contributions to this special issue.

Extracellular Release of ILEI/FAM3C and Amyloid-β Is Associated with the Activation of Distinct Synapse Subpopulations.

Background: Brain amyloid-β (Aβ) peptide is released into the interstitial fluid (ISF) in a neuronal activity-dependent manner, and Aβ deposition in Alzheimer's disease (AD) is linked to baseline neuronal activity. Although the intrinsic mechanism for Aβ generation remains to be elucidated, interleukin-like epithelial-mesenchymal transition inducer (ILEI) is a candidate for an endogenous Aβ suppressor.

Objective: This study aimed to access the mechanism underlying ILEI secretion and its effect on Aβ production in the brain.

A novel mode of interaction between intrinsically disordered proteins.

An increasing number of proteins, which have neither regular secondary nor well-defined tertiary structures, have been found to be present in cells. The structure of these proteins is highly flexible and disordered under physiological (native) conditions, and they are called "intrinsically disordered" proteins (IDPs). Many of the IDPs are involved in interactions with other biomolecules such as DNA, RNA, carbohydrates, and proteins.

Lipid class composition of membrane and raft fractions from brains of individuals with Alzheimer's disease.

Perturbation of the homeostasis of brain membrane lipids has been implicated in the pathomechanism of Alzheimer's disease (AD). The ε4 allele of the apolipoprotein E gene () confers an increased risk, in a dosage-dependent manner, for brain amyloid-β accumulation and the development of sporadic AD. An effect of the genotype on brain lipid homeostasis may underlie the AD risk associated with the ε4 allele.

Identification of heteromolecular binding sites in transcription factors Sp1 and TAF4 using high-resolution nuclear magnetic resonance spectroscopy.

The expression of eukaryotic genes is precisely controlled by interactions between general transcriptional factors and promoter-specific transcriptional activators. The fourth element of TATA-box binding protein-associated factor (TAF4), an essential subunit of the general transcription factor TFIID, serves as a coactivator for various promoter-specific transcriptional regulators. Interactions between TAF4 and site-specific transcriptional activators, such as Sp1, are important for regulating the expression levels of genes of interest.

Interaction between intrinsically disordered regions in transcription factors Sp1 and TAF4.

The expression of eukaryotic genes is precisely controlled by specific interactions between general transcription initiation factors and gene-specific transcriptional activators. The general transcription factor TFIID, which plays an essential role in mediating transcriptional activation, is a multisubunit complex comprising the TATA box-binding protein (TBP) and multiple TBP-associated factors (TAFs). On the other hand, biochemical and genetic approaches have shown that the promoter-specific transcriptional activator Sp1 has the ability to interact with one of the components of TFIID, the TBP-associated factor TAF4.

Interaction between isolated transcriptional activation domains of Sp1 revealed by heteronuclear magnetic resonance.

The promoter-specific transcription factor Sp1 is expressed ubiquitously, and plays a primary role in the regulation of the expression of many genes. Domains A and B located in the N-terminal half of the protein are characterized by glutamine-rich (Q-rich) sequences. These Q-rich domains have been shown to be involved in the interaction between Sp1 and different classes of nuclear proteins, such as TATA-binding protein associated factors.

Interspecies and intraspecies variations in the serotonin transporter gene intron 3 VNTR in nonhuman primates.

A variable number of tandem repeat (VNTR) polymorphism based on a 16 or 17-bp unit has been reported in the third intron of the human serotonin transporter gene (5-HTT). VNTRs have been shown to affect the transcriptional activity of genes, and VNTR polymorphisms possibly influence human personality and several psychoneurological disorders. To estimate the changes that occurred in the VNTRs during primate evolution, we amplified and sequenced the regions that corresponded to the human VNTRs in various primate species, including apes, Old World monkeys, and New World monkeys.

Comparison of androgen receptor CAG and GGN repeat length polymorphism in humans and apes.

Two polymorphic trinucleotide repeats of human androgen receptor gene (hAR), CAG and GGN which encode glutamine and glycine, have been shown to be associated with human diseases. The number of repeats ranges from 8 to 35 for the CAG and from 10 to 30 for the GGN in human populations. Longer CAG repeats are associated with reduced hAR transcriptional activity, spinal bulbar muscular atrophy and lower cognitive function in older men, whereas shorter CAG repeats are associated with increased risk of prostate cancer and infertility in men.