ATP promotes protein coacervation through conformational compaction.

ATP has been recognized as a hydrotrope in the phase separation process of intrinsically disordered proteins (IDPs). Surprisingly, when using the disordered RG/RGG-rich motif from HNRNPG protein as a model system, we discover a biphasic relationship between the ATP concentration and IDP phase separation. We show that at a relatively low ATP concentration, ATP dynamically interacts with the IDP, which neutralizes protein surface charges, promotes intermolecular interactions, and consequently promotes phase separation. We further demonstrate that ATP induces a compact conformation of the IDP, accounting for the reduced solvent exchange rate and lower compression ratio during phase separation. As ATP concentration increases, its hydrotropic properties emerge, leading to the dissolution of the phase-separated droplets. Our finding uncovers a complex mechanism by which ATP molecules modulate the structure, interaction, and phase separation of IDPs, and accounts for the distinct phase separation behaviors for the charge-rich RGG motif and other low-complexity IDPs.

The Relationship Between Racial Attitudes and Disordered Eating Behaviors in Black Men and Black Women.

OBJECTIVE: Black individuals remain underrepresented in disordered eating research, despite evidence that both Black men and women present with disordered eating behaviors. Culturally-informed theoretical frameworks suggest that these behaviors may be linked to race-related sociocultural experiences, such as aspects of racial identity. While studies have focused on racial identity commitment, the association between attitudes toward one's racial identity and disordered eating remains underexplored. The present study examines whether positive attitudes toward one's Blackness and Black culture are associated with disordered eating. METHOD: In a cross-sectional online sample of Black men and women (N = 458), we measured self-reported attitudes toward Blackness (i.e., centrality and private regard) and disordered eating behaviors (i.e., purging, binge eating, excessive exercise, and drive for thinness). RESULTS: In pre-registered linear regression models, private regard was negatively associated with purging and binge eating. Across all models, centrality was not associated with disordered eating. On average, Black women reported greater drive for thinness whereas Black men reported higher excessive exercise scores. DISCUSSION: This is the first study to demonstrate associations between racial attitudes and disordered eating among Black men and women. Our findings affirm unique correlates of disordered eating among Black people and suggest that positive attitudes toward one's Blackness and Black culture may be a protective factor against the development of disordered eating.

Extreme Electron-Photon Interaction in Disordered Perovskites.

The interaction of light with solids can be dramatically enhanced owing to electron-photon momentum matching. This mechanism manifests when light scattering from nanometer-sized clusters including a specific case of self-assembled nanostructures that form a long-range translational order but local disorder (crystal-liquid duality). In this paper, a new strategy based on both cases for the light-matter-interaction enhancement in a direct bandgap semiconductor - lead halide perovskite CsPbBr3 - by using electric pulse-driven structural disorder, is addressed. The disordered state allows the generation of confined photons, and the formation of an electronic continuum of static/dynamic defect states across the forbidden gap (Urbach bridge). Both mechanisms underlie photon-momentum-enabled electronic Raman scattering (ERS) and single-photon anti-Stokes photoluminescence (PL) under sub-band pump. PL/ERS blinking is discussed to be associated with thermal fluctuations of cross-linked [PbBr6]4- octahedra. Time-delayed synchronization of PL/ERS blinking causes enhanced spontaneous emission at room temperature. These findings indicate the role of photon momentum in enhanced light-matter interactions in disordered and nanostructured solids.

Nucleoporin Nsp1 surveils the phase state of FG-Nups.

Transport through the nuclear pore complex (NPC) relies on intrinsically disordered FG-nucleoporins (FG-Nups) forming a selective barrier. Away from the NPC, FG-Nups readily form condensates and aggregates, and we address how this behavior is surveilled in cells. FG-Nups, including Nsp1, together with the nuclear transport receptor Kap95, form a native daughter cell-specific cytosolic condensate in yeast. In aged cells, this condensate disappears as cytosolic Nsp1 levels decline. Biochemical assays and modeling show that Nsp1 is a modulator of FG-Nup condensates, promoting a liquid-like state. Nsp1's presence in the cytosol and condensates is critical, as a reduction of cytosolic levels in young cells induces NPC defects and a general decline in protein quality control that quantitatively mimics aging phenotypes. These phenotypes can be rescued by a cytosolic form of Nsp1. We conclude that Nsp1 is a phase state regulator that surveils FG-Nups and impacts general protein homeostasis.

Junior athletes' nutritional demands: a narrative review of consumption and prevalence of eating disorders.

Information regarding the dietary requirements and consumption of young athletes is limited. Hence, the aim of this narrative review is to provide a comprehensive combination of research and review papers on the nutritional status of young athletes aged 5-18 years old, as well as quantitative, qualitative, wholesome foods, food choices, and eating disordered data concerning the dietary requirements for growing young athletes. This study involved systematic searches of electronic databases, including Google Scholar, PubMed, Science Direct, Scopus, and Web of Science. The specific criteria for identifying research papers published in English from July 1980 until May 2024 were included. Only 48 studies out of 1,262 were included in this narrative review. The findings of this study suggest that, compared with adults, junior athletes need a unique approach to meet their dietary needs. Growth, development, and general athletic performance depend on macronutrients, as they are vital nutrients for young active athletes. However, research on enhancing junior athletes' performance is still in progress, and studies on hydration status, and eating disorders are limited.

SHARK enables sensitive detection of evolutionary homologs and functional analogs in unalignable and disordered sequences.

Intrinsically disordered regions (IDRs) are structurally flexible protein segments with regulatory functions in multiple contexts, such as in the assembly of biomolecular condensates. Since IDRs undergo more rapid evolution than ordered regions, identifying homology of such poorly conserved regions remains challenging for state-of-the-art alignment-based methods that rely on position-specific conservation of residues. Thus, systematic functional annotation and evolutionary analysis of IDRs have been limited, despite them comprising ~21% of proteins. To accurately assess homology between unalignable sequences, we developed an alignment-free sequence comparison algorithm, SHARK (Similarity/Homology Assessment by Relating K-mers). We trained SHARK-dive, a machine learning homology classifier, which achieved superior performance to standard alignment-based approaches in assessing evolutionary homology in unalignable sequences. Furthermore, it correctly identified dissimilar but functionally analogous IDRs in IDR-replacement experiments reported in the literature, whereas alignment-based tools were incapable of detecting such functional relationships. SHARK-dive not only predicts functionally similar IDRs at a proteome-wide scale but also identifies cryptic sequence properties and motifs that drive remote homology and analogy, thereby providing interpretable and experimentally verifiable hypotheses of the sequence determinants that underlie such relationships. SHARK-dive acts as an alternative to alignment to facilitate systematic analysis and functional annotation of the unalignable protein universe.

Disordered Eating in Early Adolescence: Disparities Among Minoritised Youth.

BACKGROUND: Disordered eating in early adolescence impacts development, with long-term health implications. Minoritised adolescents might be at higher risk of disordered eating due to minority stress, but most research has focused on White, heterosexual, cisgender individuals; less is known about disordered eating among minoritised adolescents. We examined sexual, gender, racial, and ethnic identities in relation to disordered eating in early adolescence. METHOD: Using 2-year follow-up data from adolescents ages 10-14 in the Adolescent Brain Cognitive Development Study (N = 9385), we examined associations between sexual, gender, racial, and ethnic identities and past-2 week disordered eating (preoccupation with weight, weight control behaviors, and binge eating). RESULTS: Compared to heterosexual peers, gay/bisexual adolescents had higher odds of all three outcomes (AOR 1.90-3.32); those "questioning" their sexual identity had higher odds of preoccupation with weight (AOR 1.82) and binge eating (AOR 2.53). Compared to cisgender adolescents, transgender adolescents had higher odds of binge eating (AOR 2.62); those "questioning" their gender identity had higher odds of preoccupation with weight (AOR 2.45). Adolescents whose racial identity was categorised as "Another" had higher odds of preoccupation with weight (AOR 1.46) and weight control behaviors (AOR 1.58) compared to White adolescents. Finally, Hispanic adolescents had higher odds of all disordered eating outcomes than non-Hispanic adolescents (AOR 1.25-1.59). DISCUSSION: This study is among the first to reveal disparities in disordered eating among minoritised early adolescents. Further examination of these disparities can inform future interventions. Healthcare providers are encouraged to screen for disordered eating, recognising that minoritised early adolescents may be at risk.

Beyond RNA binding domains: determinants of protein-RNA binding.

RNA binding proteins (RBPs) are composed of RNA binding domains (RBDs) often linked via intrinsically disordered regions (IDRs). Structural and biochemical analysis have shown that disordered linkers contribute to RNA binding by orienting the adjacent RBDs and also characterized certain disordered repeats that directly contact the RNA. However, the relative contribution of IDRs and predicted RBDs to the in-vivo binding pattern is poorly explored. Here, we upscaled the RNA tagging method to map the transcriptome-wide binding of sixteen RBPs in budding yeast. We then performed extensive sequence mutations to distinguish binding determinants within predicted RBDs and the surrounding IDRs in eight of these. The majority of the predicted RBDs tested were not individually essential for mRNA binding, while multiple IDRs that lacked predicted RNA binding potential appeared essential for binding affinity or specificity. Our results provide new insights into the function of poorly studied RBPs and emphasize the complex and distributed encoding of RBP-RNA interaction in-vivo.

TDP-43 Amyloid Fibril Formation via Phase Separation-Related and -Unrelated Pathways.

Intrinsically disordered regions (IDRs) in proteins can undergo liquid-liquid phase separation (LLPS) for functional assembly, but this increases the chance of forming disease-associated amyloid fibrils. Not all amyloid fibrils form through LLPS however, and the importance of LLPS relative to other pathways in fibril formation remains unclear. We investigated this question in TDP-43, a motor neuron disease and dementia-causing protein that undergoes LLPS, using thioflavin T (ThT) fluorescence, NMR, transmission electron microscopy (TEM), and wide-angle X-ray scattering (WAXS) experiments. Using a fluorescence probe modified from ThT strategically designed for targeting protein assembly rather than ß-sheets and supported by TEM images, we propose that the biphasic ThT signals observed under LLPS-favoring conditions are due to the presence of amorphous aggregates. These aggregates represent an intermediate state that diverges from the direct pathway to ß-sheet-dominant fibrils. Under non-LLPS conditions in contrast (at low pH or at physiological conditions in a construct with key LLPS residues removed), the protein forms a hydrogel. Real-time WAXS data, ThT signals, and TEM images collectively demonstrate that the gelation process circumvents LLPS and yet still results in the formation of fibril-like structural networks. We suggest that the IDR of TDP-43 forms disease-causing amyloid fibrils regardless of the formation pathway. Our findings shed light on why both LLPS-promoting and LLPS-inhibiting mutants are found in TDP-43-related diseases.

Preparation and Performance Investigation of Carbon-Coated Li1.2Mn0.2Ti0.6O2/C Cathode Materials.

Mn-based cation disordered rock-salt (DRX) cathode materials exhibit promising application prospects due to their cost-effectiveness and high specific capacity. However, the synthesis methods commonly employed for these materials rely on the solid-state reaction method and mechanochemistry method, primarily attributed to the influence of low-valence states of Mn. Currently, sol-gel approaches for preparing Mn-based DRX cathode materials are limited to systems involving Mn3+. Furthermore, there is a paucity of research regarding the modification of Mn-based DRX. To address this concern, the submicrometer-sized carbon-coated Li1.2Mn0.2Ti0.6O2/C materials were synthesized via a one-step sintering process using the sol-gel method with sucrose as the carbon source, resulting in smaller particle sizes compared to those prepared by the solid-state reaction at the same temperature. When employed as a cathode material for lithium batteries, samples prepared with 10 wt % sucrose exhibited exceptional cycling stability by delivering an initial discharge specific capacity of 119.6 mA h g-1 (at a current density of 20 mA g-1). After 20 charge-discharge cycles, a reversible specific capacity of 91.0 mA h g-1 was achieved, with a capacity retention rate of 76.1%. This approach provides distinctive insights and strategies for the preparation and modification of manganese-titanium-based disordered rock-salt cathode materials.

C. elegans epicuticlins define specific compartments in the apical extracellular matrix and function in wound repair.

The apical extracellular matrix (aECM) of external epithelia often contains lipid-rich outer layers that contribute to permeability barrier function. The external aECM of nematodes is known as the cuticle and contains an external lipid-rich layer, the epicuticle. Epicuticlins are a family of tandem repeat cuticle proteins of unknown function. Here, we analyze the localization and function of the three C. elegans epicuticlins (EPIC proteins). EPIC-1 and EPIC-2 localize to the surface of the cuticle near the outer lipid layer, as well as to interfacial cuticles and adult-specific struts. EPIC-3 is expressed in dauer larvae and localizes to interfacial aECM in the buccal cavity. Skin wounding in the adult induces epic-3 expression, and EPIC proteins localize to wound sites. Null mutants lacking EPIC proteins are viable with reduced permeability barrier function and normal epicuticle lipid mobility. Loss of function in epic genes modifies the skin blistering phenotypes of bli mutants and reduces survival after skin wounding. Our results suggest EPIC proteins define specific cortical compartments of the aECM and promote wound repair.

Loss of Control Eating in Adults With Impulsive and/or Inattentive Tendencies.

OBJECTIVE: Previous research has tended to consider impulsive, inattentive, and loss of control eating (LOC) tendencies as symptoms of greater pathologies in treatment-seeking samples. However, inattentive and impulsive tendencies and LOC often co-occur. Although LOC is an important diagnostic component of disordered eating (ED), it has recently been argued to be a dysregulated eating behavior in its own right. The purpose of the current self-report study was, therefore, to investigate the association between impulsive and inattentive tendencies and LOC in adults after accounting for ED. METHOD: A community sample of 516 adults was surveyed online about their inattentive and impulsive tendencies, LOC, and ED behaviors. RESULTS: A hierarchical multiple linear regression revealed ED, inattentive, and impulsive symptoms to be independent, significant, positive predictors of LOC. DISCUSSION: These findings suggest that the levels of inattentive and, to a lesser extent, impulsive tendencies are significantly associated with LOC in adults, even after ED is accounted for. Moreover, inattentive tendencies were found to be more significantly associated with LOC than impulsive tendencies. These are novel and important findings that can be used to inform both clinicians and individuals with inattentive and impulsive tendencies alike of this association. Considering the well-documented adverse health and wellbeing outcomes associated with LOC, future feasibility trials are needed aimed at treating this co-occurrence.

An Objective Study to Establish Incidence of True Obstructive Sleep Apnoea (OSA) in Sleep Disordered Breathing in the Paediatric Age Group and Assessment of Benefit of Surgery (Tonsillectomy and Adenoidectomy) in Non Responders to Medical Treatment in Mild OSA.

Obstructive sleep apnea (OSA) is identified by instances of either full or partial collapse of the airway during sleep, leading to reduced oxygen levels or awakening from sleep. This disruption causes interrupted and insufficient sleep, impacting cardiovascular well-being, mental health, and overall quality of life. Pediatric OSA is more challenging to diagnose and a single apnoea is considered to be significant in this age group. A hospital based prospective study with 100 children between the ages of 4 and 12 years with sleep disordered breathing. Evaluated for the severity of obstructive sleep apnea and also assessed if surgery was beneficial to treat OSA in mild cases. General physical examination, evaluation of facial/oral features were conducted to rule out adenoid facies. Additionally, ENT examination was conducted. Medical history and lateral neck radiographs were reviewed, and the paediatric sleep questionnaire was administered to evaluate neurobehavioral morbidities associated with OSA. These children were evaluated for sleep disorders by conducting the polysomnography. Pediatric sleep questionnaire was also administered. The scoring and results analysis were conducted according to standardised guidelines provided by the American association for sleep medicine. Furthermore, medical management protocols were outlined, including a 6-week course of intranasal steroids and leukotriene receptor antagonist therapy, with consideration of adenotonsillectomy for patients failing medical therapy. In our study on paediatric obstructive sleep apnea (OSA), medical treatment significantly reduced clinical symptom scores in cases of mild OSA, as evidenced by pre- and post-parental sleep questionnaire scores of 23.62 ± 8.24 and 13.55 ± 6.05, respectively (paired samples test, P = 0.00). Similarly, both the pre- and post-Apnoea/Hypopnoea Index (AHI) scores (2.278 ± 1.5658 and 1.19 ± 1.420) and central sleep apnea index scores (1.252 ± 0.8972 and 0.61 ± 0.815) significantly improved post-treatment (paired samples test, P = 0.03, respectively). Additionally, significant changes were observed in tonsillar grade after the 12-week medication course, and sleep architecture showed notable improvement during the repeat follow-up study. These findings highlight the efficacy of treatment interventions in alleviating symptoms and enhancing sleep efficiency in paediatric OSA. The findings of this study underscore the efficacy of a medical management using intranasal corticosteroids and oral montelukast in mitigating the severity of mild obstructive sleep apnea (OSA) in children. This research substantiates the therapeutic value of corticosteroids and oral montelukast in paediatric patients with mild OSA, offering compelling evidence for their use as beneficial interventions in this population. Supplementary Information: The online version contains supplementary material available at 10.1007/s12070-024-04813-6.

Evaluating Positional Obstructive Sleep Apnea in Children: Prevalence, Characteristics, and Risk Factors.

Purpose: This study investigates the prevalence, risk factors, and clinical characteristics of positional obstructive sleep apnea (POSA) among pediatric patients diagnosed with obstructive sleep apnea (OSA). Patients and Methods: A total of 1,236 children aged 0 to 17 years who underwent nocturnal polysomnography (PSG) and completed the Sleep Questionnaire were included. After excluding those with an AHI <1, neurological or muscular disorders, or insufficient sleep time in specific positions, 908 patients remained: 158 with POSA and 750 with non-positional OSA (NPOSA). Propensity score matching (PSM) was applied at a 1:2 ratio, resulting in a final sample of 153 POSA and 306 NPOSA patients. Data analyses were performed using R software (version 4.2.3). Results: The prevalence of POSA was 12.8%. After PSM, patients with POSA had a lower overall AHI (8.66 vs 10.30), REM-AHI (14.30 vs 17.40), and NREM-AHI (7.43 vs 8.77) compared to those with NPOSA. POSA patients also had a shorter total sleep time (411 vs 427 minutes), spent less time in the supine position (168 vs 225 minutes), and more time in non-supine positions (241 vs 202 minutes) than NPOSA patients. Additionally, while the supine AHI was higher in POSA patients (15.60 vs 10.30), the non-supine AHI was lower (5.00 vs 11.00) compared to NPOSA patients. The minimum oxygen saturation was slightly higher in POSA patients (0.88 vs 0.87). All differences were statistically significant (P < 0.05). Risk factors for POSA included mild OSA, allergic rhinitis, non-allergic rhinitis, and obesity. Conclusion: The prevalence of POSA in children is lower than in adults, and its severity is less than that of NPOSA. Compared to NPOSA patients, POSA patients had significantly higher AHI during supine sleep and lower AHI during non-supine sleep. POSA patients also spent more time in non-supine positions, suggesting that avoiding supine sleep may help reduce apnea events. These findings highlight the importance of monitoring and managing sleep posture in POSA patients.

Potential pathways to the onset and development of eating disorders in people with overweight and obesity: A scoping review.

OBJECTIVE: To describe pathways to eating disorder (ED) development that have been evaluated in people with overweight and obesity. METHODS: Four databases were searched to identify studies testing ED development models in adolescents (10-19 years) or adults (>19 years) with overweight and obesity. Explanatory variables were thematically grouped into constructs to describe pathways to each ED outcome. RESULTS: Of 2226 studies screened, 46 (10 adolescent; 36 adult) were included. Study samples were predominantly female, ranging from 22 to 2236 participants and mean age 12.3 to 56.0 years. In total, 207 explanatory variables were grouped into 18 constructs to summarize 107 pathways that were identified. The most common ED outcome was binge eating (n = 24 studies), followed by global ED psychopathology (n = 10 studies). Across pathways to ED development, negative affect was the most proposed construct, followed by preoccupation with weight/shape and weight stigma. CONCLUSION: Pathways to ED development in people with overweight and obesity are complex and may include more than 18 different explanatory factors of which negative affect, preoccupation with weight/shape, and weight stigma are the most common. More research on adolescents, males, and the spectrum of ED in diverse populations is required for early identification and intervention.

Isoform-specific C-terminal phosphorylation drives autoinhibition of Casein kinase 1.

Casein kinase 1δ (CK1δ) controls essential biological processes including circadian rhythms and wingless-related integration site (Wnt) signaling, but how its activity is regulated is not well understood. CK1δ is inhibited by autophosphorylation of its intrinsically disordered C-terminal tail. Two CK1 splice variants, δ1 and δ2, are known to have very different effects on circadian rhythms. These variants differ only in the last 16 residues of the tail, referred to as the extreme C termini (XCT), but with marked changes in potential phosphorylation sites. Here, we test whether the XCT of these variants have different effects in autoinhibition of the kinase. Using NMR and hydrogen/deuterium exchange mass spectrometry, we show that the δ1 XCT is preferentially phosphorylated by the kinase and the δ1 tail makes more extensive interactions across the kinase domain. Mutation of δ1-specific XCT phosphorylation sites increases kinase activity both in vitro and in cells and leads to changes in the circadian period, similar to what is reported in vivo. Mechanistically, loss of the phosphorylation sites in XCT disrupts tail interaction with the kinase domain. δ1 autoinhibition relies on conserved anion-binding sites around the CK1 active site, demonstrating a common mode of product inhibition of CK1δ. These findings demonstrate how a phosphorylation cycle controls the activity of this essential kinase.

Structural study of the intrinsically disordered tardigrade damage suppressor protein (Dsup) and its complex with DNA.

Studies of proteins, found in one of the most stress-resistant animals tardigrade Ramazzottius varieornatus, aim to reveal molecular principles of extreme tolerance to various types of stress and developing applications based on them for medicine, biotechnology, pharmacy, and space research. Tardigrade DNA/RNA-binding damage suppressor protein (Dsup) reduces DNA damage caused by reactive oxygen spices (ROS) produced upon irradiation and oxidative stresses in Dsup-expressing transgenic organisms. This work is focused on the determination of structural features of Dsup protein and Dsup-DNA complex, which refines details of protective mechanism. For the first time, intrinsically disordered nature of Dsup protein with highly flexible structure was experimentally proven and characterized by the combination of small angle X-ray scattering (SAXS) technique, circular dichroism spectroscopy, and computational methods. Low resolution models of Dsup protein and an ensemble of conformations were presented. In addition, we have shown that Dsup forms fuzzy complex with DNA.

Sex Differences in Obstructive Patterns on Drug-Induced Sleep Endoscopy.

OBJECTIVE: To identify and characterize sex differences in collapse patterns on drug-induced sleep endoscopy (DISE) in patients with obstructive sleep apnea (OSA). STUDY DESIGN: Retrospective cohort analysis. SETTING: An outpatient tertiary care academic medical center. METHODS: A retrospective cohort study at a single tertiary care institution was performed from 2020 to 2023. All adult patients who underwent a DISE were included in this study. Univariate and multivariate analyses were used to compare differences between males and females on DISE. RESULTS: 117 patients who underwent DISE were included in this study, including 30% females (n = 35). The average age was 54.7 years (SD 15.2), mean BMI was 28.6 kg/m2 (SD 4.1), and mean apnea-hypopnea index (AHI) was 32.3 events per hour (SD 21.3). Most patients had severe OSA (48.7%). There was no difference in palatine or lingual tonsil size between sexes. On DISE, a significantly lower proportion of females demonstrated complete oropharyngeal lateral wall collapse (25.7% females vs 51.2% males, P = .008). Multivariate analysis revealed that male sex was independently associated with the presence of complete collapse at the oropharynx (odds ratio [OR] 2.55, 95% confidence interval [CI] [0.005-1.868], P = .048) but not at other levels. Additionally, higher BMI was associated with any collapse (partial or complete) at the oropharynx (OR 1.30, 95% CI [0.131-0.392], P < .001). CONCLUSION: This study demonstrates that a lower proportion of females have complete oropharyngeal lateral wall collapse even when controlling for BMI and AHI. Additional studies are needed to better understand the differences in OSA physiology between the sexes.

Exploring the dynamics and interactions of the N-myc transactivation domain through solution NMR.

Myc proteins are transcription factors crucial for cell proliferation. They have a C-terminal domain that mediates Max and DNA binding, and an N-terminal disordered region culminating in the transactivation domain (TAD). The TAD participates in many protein-protein interactions, notably with kinases that promote stability (Aurora-A) or degradation (ERK1, GSK3) via the ubiquitin-proteasome system. We probed the structure, dynamics and interactions of N-myc TAD using nuclear magnetic resonance (NMR) spectroscopy following its complete backbone assignment. Chemical shift analysis revealed that N-myc has two regions with clear helical propensity: Trp77-Glu86 and Ala122-Glu132. These regions also have more restricted ps-ns motions than the rest of the TAD, and, along with the phosphodegron, have comparatively high transverse (R2) 15N relaxation rates, indicative of slower timescale dynamics and/or chemical exchange. Collectively these features suggest differential propensities for structure and interaction, either internal or with binding partners, across the TAD. Solution studies on the interaction between N-myc and Aurora-A revealed a previously uncharacterised binding site. The specificity and kinetics of sequential phosphorylation of N-myc by ERK1 and GSK3 were characterised using NMR and resulted in no significant structural changes outside the phosphodegron. When the phosphodegron was doubly phosphorylated, N-myc formed a robust interaction with the Fbxw7-Skp1 complex, but mapping the interaction by NMR suggests a more extensive interface. Our study provides foundational insights into N-myc TAD dynamics and a backbone assignment that will underpin future work on the structure, dynamics, interactions and regulatory post-translational modifications of this key oncoprotein.