Designing active RNF4 monomers by introducing a tryptophan: avidity towards E2~Ub conjugates dictates the activity of ubiquitin RING E3 ligases

Ubiquitin RING E3 ligases (E3s) catalyze ubiquitin (Ub) transfer to their substrates by engaging E2~Ub intermediates with the help of their RING domains. Different E3s have been found to contain a conserved tryptophan residue in their RING that plays an essential role in E2 binding and, hence, enzymatic activity. Many active E3s, however, lack this specific residue. We mined through the existing data to observe that the conservation of the tryptophan and quaternary organization of the RING domains are remarkably correlated. Monomeric RINGs possess the tryptophan while all well-characterized dimeric RINGs, except RNF8, contain other amino acid residues. Biochemical analyses on representative E3s and their mutants reveal that the tryptophan is essential for optimal enzymatic activity of monomeric RINGs whereas dimeric E3s with tryptophan display hyperactivity. Most critically, the introduction of the tryptophan restores the activity of inactive monomeric RNF4 mutants, an obligatory dimeric E3. Binding studies indicate that monomeric RINGs retained the tryptophan for their optimal functionality to compensate for weak Ub binding. On the other hand, tryptophan was omitted from dimeric RINGs during the course of evolution to prevent unwanted modifications and allow regulation of their activity through oligomerization.
Source: Biochemical Journal - Category: Biochemistry Authors: Tags: Research Articles Source Type: research

Related Links:

The ability to start and delay a task differs significantly between kids with attention deficit-hyperactivity disorder and typically developing children, new research suggests.Medscape Medical News
Source: Medscape Psychiatry Headlines - Category: Psychiatry Tags: Neurology & Neurosurgery News Source Type: news
Conclusions: Bipolar disorder is common among primary care patients presenting with depression; it is often treated exclusively in primary care. Clinicians should be alert for symptoms of bipolar disorder in undiagnosed patients, know what symptoms probabilistically suggest bipolar versus unipolar depression, have expertise in providing ongoing treatment to diagnosed patients, and be knowledgeable about managing common medication-related side effects and comorbidities. Prompt and accurate diagnosis is critical. PMID: 31311335 [PubMed - as supplied by publisher]
Source: Current Medical Research and Opinion - Category: Research Tags: Curr Med Res Opin Source Type: research
Medication for attention-deficit/hyperactivity disorder (ADHD) may help lower the risk of unintentional injuries in children and adolescents with ADHD, astudy in theJournal of the American Academy of Child&Adolescent Psychiatryhas found.“[Prior studies] suggest that ADHD is associated with a 40% to 50% increase in the risk of injuries in children and adolescents. Pharmacological treatment for ADHD has been reported to be effective for core symptoms and cognitive deficits associated with ADHD. Hence it may be hypothesized that, by reducing distractibility, impulsivity, and overactivity, ADHD medication may prevent...
Source: Psychiatr News - Category: Psychiatry Tags: ADHD ADHD medication attention-deficit/hyperactivity disorder injury Journal of the American Academy of Child & Adolescent Psychiatry Source Type: research
Publication date: Available online 17 July 2019Source: Journal of Clinical NeuroscienceAuthor(s): Zeynep Selen Karalok, Zeynep Öztürk, Altan GunesAbstractThe aim of this study is to evaluate the abnormal cortical structures associated with newly diagnosed benign epilepsy with centrotemporal spikes (BECTS) patients and assessed the effects of comorbid attention-deficit/hyperactivity (ADHD) on these abnormalities. Newly diagnosed BECTS patients (n = 33, 23 males) and age-matched healthy controls (n = 48) were evaluated by surface and volumetric MRI. CAT12 toolbox (HYPERLINK “http://www.neuro.uni-jena....
Source: Journal of Clinical Neuroscience - Category: Neuroscience Source Type: research
THURSDAY, July 18, 2019 -- Athletes with attention-deficit/hyperactivity disorder (ADHD) with concussion seem to have longer recovery than controls, regardless of their psychostimulant medication status, according to a study presented at the...
Source: - Pharma News - Category: Pharmaceuticals Source Type: news
A 2-year-old male pediatric patient experienced a partial occlusion of the internal carotid and subsequent asphyxiation resulting in hypoxic brain injury that was later misdiagnosed as primary attention deficient hyperactivity disorder (ADHD). Imaging anal...
Source: SafetyLit - Category: International Medicine & Public Health Tags: Age: Infants and Children Source Type: news
Authors: Tran K, Wu J Abstract A 2-year-old male pediatric patient experienced a partial occlusion of the internal carotid and subsequent asphyxiation resulting in hypoxic brain injury that was later misdiagnosed as primary attention deficient hyperactivity disorder (ADHD). Imaging analyses using diffusion tensor imaging (DTI), positron emission tomography (PET), and magnetic resonance imaging (MRI) quantitative volumetrics (QV) were used nine years following the incident to identify whether his development of ADHD is of a primary heritability or secondary hypoxic brain injury sequelae. The patient's DTI analysis g...
Source: Brain Injury - Category: Neurology Tags: Brain Inj Source Type: research
The involvement of mitochondrial dysfunction in the pathophysiology of attention-deficit hyperactivity disorder (ADHD) has been suggested in several reports. Mitochondrial DNA (mtDNA) copy number, as well as methylation of the D-loop region and peroxisome-proliferator-activated receptor γ co-activator-1α (PPARGC1A), are considered biomarkers for mitochondrial dysfunction. We compared the mtDNA copy number and methylation ratio of the D-loop region and PPARGC1A between ADHD patients and controls. The present study included 70 subjects with ADHD and 70 age- and gender-matched healthy controls (HCs). The relative ...
Source: Frontiers in Psychiatry - Category: Psychiatry Source Type: research
ConclusionsOur results suggest that there may be similarly inefficient cognitive emotional regulation skills leading to ED in both disorders (ADHD and BPD). However, ADHD patients showed a higher use of adaptive cognitive emotional strategies and a lower level of ED than BPD patients.
Source: Borderline Personality Disorder and Emotion Dysregulation - Category: Psychiatry Source Type: research
AbstractAttention Deficit Hyperactivity Disorder (ADHD) is the most common neuropsychiatric condition in childhood and adolescence. Psychoeducation has been recommended by different guidelines as an initial treatment for ADHD, however the effects of the intervention for reducing symptoms and improving other outcomes still need to be established. This systematic review investigated the magnitude of impact that psychoeducation interventions have on various outcomes in children with ADHD. A systematic review of articles published between 1990 and 2018 was conducted of treatment outcome studies that investigated the effects of...
Source: Journal of Developmental and Physical Disabilities - Category: Disability Source Type: research
More News: Biochemistry | Hyperactivity | Study