Structural basis for hepatitis B virus restriction by a viral receptor homologue.

Macaque restricts hepatitis B virus (HBV) infection because its receptor homologue, NTCP (mNTCP), cannot bind preS1 on viral surface. To reveal how mNTCP loses the viral receptor function, we here solve the cryo-electron microscopy structure of mNTCP. Superposing on the human NTCP (hNTCP)-preS1 complex structure shows that Arg158 of mNTCP causes steric clash to prevent preS1 from embedding onto the bile acid tunnel of NTCP.

Evaluation of a Novel Virtual Reality Simulated Alternate Cover Test to Assess Strabismus: A Prospective, Masked Study.

Purpose: A sensorimotor examination is the gold standard for strabismus diagnosis and quantification but requires a highly skilled examiner and may be limited by a child's cooperation. Virtual reality (VR) employs eye-tracking technology to monitor eye position and may be able to measure strabismus. The aim of this study was to assess a prototype VR-simulated alternate cover test to detect and measure strabismus.

The fungal diversity in the lungs of children with cystic fibrosis captured by sputum-induction and bronchoalveolar lavage.

Background: The prevalence of fungi in cystic fibrosis (CF) lung infections is poorly understood and studies have focused on adult patients. We investigated the fungal diversity in children with CF using bronchoalveolar lavage (BAL) and induced sputum (IS) samples to capture multiple lung niches.

Methods: Sequencing of the fungal ITS2 region and molecular mycobiota diversity analysis was performed on 25 matched sets of BAL-IS samples from 23 children collected as part of the CF-SpIT study (UKCRN14615; ISRCTNR12473810).

The unique allosteric property of crocodilian haemoglobin elucidated by cryo-EM.

The principal effect controlling the oxygen affinity of vertebrate haemoglobins (Hbs) is the allosteric switch between R and T forms with relatively high and low oxygen affinity respectively. Uniquely among jawed vertebrates, crocodilians possess Hb that shows a profound drop in oxygen affinity in the presence of bicarbonate ions. This allows them to stay underwater for extended periods by consuming almost all the oxygen present in the blood-stream, as metabolism releases carbon dioxide, whose conversion to bicarbonate and hydrogen ions is catalysed by carbonic anhydrase.

Structural basis for the recognition of human hemoglobin by the heme-acquisition protein Shr from Streptococcus pyogenes.

In Gram-positive bacteria, sophisticated machineries to acquire the heme group of hemoglobin (Hb) have evolved to extract the precious iron atom contained in it. In the human pathogen Streptococcus pyogenes, the Shr protein is a key component of this machinery. Herein we present the crystal structure of hemoglobin-interacting domain 2 (HID2) of Shr bound to Hb.

Structural basis for ligand recognition and signaling of hydroxy-carboxylic acid receptor 2.

Hydroxycarboxylic acid receptors (HCAR1, HCAR2, and HCAR3) transduce G signaling upon biding to molecules such as lactic acid, butyric acid and 3-hydroxyoctanoic acid, which are associated with lipolytic and atherogenic activity, and neuroinflammation. Although many reports have elucidated the function of HCAR2 and its potential as a therapeutic target for treating not only dyslipidemia but also neuroimmune disorders such as multiple sclerosis and Parkinson's disease, the structural basis of ligand recognition and ligand-induced G-coupling remains unclear. Here we report three cryo-EM structures of the human HCAR2-G signaling complex, each bound with different ligands: niacin, acipimox or GSK256073.

Attention, response inhibition, and hoarding: A neuropsychological examination.

Background And Aims: The prominent cognitive-behavioral model of hoarding posits that information processing deficits contribute to hoarding disorder. Although individuals with hoarding symptoms consistently self-report attentional and impulsivity difficulties, neuropsychological tests have inconsistently identified impairments. These mixed findings may be the result of using different neuropsychological tests, tests with poor psychometric properties, and/or testing individuals in a context that drastically differs from their own homes.

Structural basis of CXC chemokine receptor 1 ligand binding and activation.

Neutrophil granulocytes play key roles in innate immunity and shaping adaptive immune responses. They are attracted by chemokines to sites of infection and tissue damage, where they kill and phagocytose bacteria. The chemokine CXCL8 (also known as interleukin-8, abbreviated IL-8) and its G-protein-coupled receptors CXCR1 and CXCR2 are crucial elements in this process, and also the development of many cancers.

Enzyme dynamics-a brief review.

Debate has been simmering for some years regarding the importance of internal thermal motions of enzymes to catalysis. Recent developments in protein design may bring resolution of the more contentious points a little closer.

Editors' roundup: April 2023.

The IUPAB journal provides a regular forum, known as the "Editors' Roundup," that is available to editorial board members of any biophysics-related journal to contribute a personal recommendation of articles appearing within their publications. This latest Issue of the Editors' Roundup carries recommendations from editorial board members associated with the following journals, , and the journal.

Development of transdiagnostic clinical risk prediction models for 12-month onset and course of eating disorders among adolescents in the community.

Objective: To develop and internally validate risk prediction models for adolescent onset and persistence of eating disorders.

Methods: N = 963 Australian adolescents (11-19 years) in the EveryBODY Study cohort completed online surveys in 2018 and 2019. Models were built to predict 12-month risk of (1) onset, and (2) persistence of a DSM-5 eating disorder.

Situational, emotional, and individual dispositions to weight gain in people with hoarding problems.

Objectives: Individuals with hoarding disorder are more likely to be overweight or obese than the general population for unknown reasons.

Methods: One hundred and twenty-nine individuals (Hoarding Group: n = 63; Control Group: n = 66) completed self-report measures and were offered snacks in a tidy and a cluttered environment in a counterbalanced order. Groups were based on the self-reporting of high or low hoarding symptoms.

Examination of bidirectional relationships between fear of negative evaluation and weight/shape concerns over 3 years: A longitudinal cohort study of Australian adolescents.

Objective: Adolescents commonly experience both fear of negative evaluation and weight/shape concerns. However, evidence concerning the prospective associations between these constructs during adolescence is limited. The current study examined the bidirectional relationships between fear of negative evaluation and weight/shape concerns over a 3-year period in adolescents.

Evolution and molecular basis of a novel allosteric property of crocodilian hemoglobin.

The extraordinary breath-hold diving capacity of crocodilians has been ascribed to a unique mode of allosterically regulating hemoglobin (Hb)-oxygenation in circulating red blood cells. We investigated the origin and mechanistic basis of this novel biochemical phenomenon by performing directed mutagenesis experiments on resurrected ancestral Hbs. Comparisons of Hb function between the common ancestor of archosaurs (the group that includes crocodilians and birds) and the last common ancestor of modern crocodilians revealed that regulation of Hb-O affinity via allosteric binding of bicarbonate ions represents a croc-specific innovation that evolved in combination with the loss of allosteric regulation by ATP binding.

Difficulties with emotion regulation and weight/shape concerns as predictors of eating disorder behaviors among adolescents.

Background: Difficulties with emotion regulation are a proposed key transdiagnostic factor of mental health difficulties, including eating disorders. However, it remains unclear whether difficulties with emotion regulation prospectively predict engagement in eating disorder behaviors. The current study examined whether difficulties with emotion regulation were associated with eating disorder behaviors after 1 year, in addition to weight and shape concerns.

Structural Basis of Sequential and Concerted Cooperativity.

Allostery is a property of biological macromolecules featuring cooperative ligand binding and regulation of ligand affinity by effectors. The definition was introduced by Monod and Jacob in 1963, and formally developed as the "concerted model" by Monod, Wyman, and Changeux in 1965. Since its inception, this model of cooperativity was seen as distinct from and not reducible to the "sequential model" originally formulated by Pauling in 1935, which was developed further by Koshland, Nemethy, and Filmer in 1966.

NMR-guided directed evolution.

Directed evolution is a powerful tool for improving existing properties and imparting completely new functionalities to proteins. Nonetheless, its potential in even small proteins is inherently limited by the astronomical number of possible amino acid sequences. Sampling the complete sequence space of a 100-residue protein would require testing of 20 combinations, which is beyond any existing experimental approach.

Unraveling the Photoactivation Mechanism of a Light-Activated Adenylyl Cyclase Using Ultrafast Spectroscopy Coupled with Unnatural Amino Acid Mutagenesis.

The hydrogen bonding network that surrounds the flavin in blue light using flavin adenine dinucleotide (BLUF) photoreceptors plays a crucial role in sensing and communicating the changes in the electronic structure of the flavin to the protein matrix upon light absorption. Using time-resolved infrared spectroscopy (TRIR) and unnatural amino acid incorporation, we investigated the photoactivation mechanism and the role of the conserved tyrosine (Y6) in the forward reaction of the photoactivated adenylyl cyclase from (OaPAC). Our work elucidates the direct connection between BLUF photoactivation and the structural and functional implications on the partner protein for the first time.

Structure of the human galanin receptor 2 bound to galanin and Gq reveals the basis of ligand specificity and how binding affects the G-protein interface.

Galanin is a neuropeptide expressed in the central and peripheral nervous systems, where it regulates various processes including neuroendocrine release, cognition, and nerve regeneration. Three G-protein coupled receptors (GPCRs) for galanin have been discovered, which is the focus of efforts to treat diseases including Alzheimer's disease, anxiety, and addiction. To understand the basis of the ligand preferences of the receptors and to assist structure-based drug design, we used cryo-electron microscopy (cryo-EM) to solve the molecular structure of GALR2 bound to galanin and a cognate heterotrimeric G-protein, providing a molecular view of the neuropeptide binding site.

Structural insights into the HBV receptor and bile acid transporter NTCP.

Around 250 million people are infected with hepatitis B virus (HBV) worldwide, and 15 million may also carry the satellite virus hepatitis D virus (HDV), which confers even greater risk of severe liver disease. The HBV receptor has been identified as sodium taurocholate co-transporting polypeptide (NTCP), which interacts directly with the first 48 amino acid residues of the N-myristoylated N-terminal preS1 domain of the viral large protein. Despite the pressing need for therapeutic agents to counter HBV, the structure of NTCP remains unsolved.

Reverse Engineering Analysis of the High-Temperature Reversible Oligomerization and Amyloidogenicity of PSD95-PDZ3.

PSD95-PDZ3, the third PDZ domain of the post-synaptic density-95 protein (MW 11 kDa), undergoes a peculiar three-state thermal denaturation (N ↔ In ↔ D) and is amyloidogenic. PSD95-PDZ3 in the intermediate state (I) is reversibly oligomerized (RO: Reversible oligomerization). We previously reported a point mutation (F340A) that inhibits both ROs and amyloidogenesis and constructed the PDZ3-F340A variant.