scholarly journals Identification of p.Met215Ile mutation of the MC4R gene in a Moroccan woman with obesity

2021 ◽  
Author(s):  
Meriem El Fessikh ◽  
HAKIM BELGHITI ◽  
ZOUHAIR ELKARHAT ◽  
HASSANIA GUERINECH ◽  
Nadia DAKKA ◽  
...  
Keyword(s):  
Morbid Obesity ◽  
Protein Structure ◽  
Hydrophobic Interactions ◽  
Rare Mutation ◽  
Mc4r Gene ◽  
Moroccan Woman

The MC4R is involved in the leptin-melanocortin pathway which mutations can lead to severe forms of obesity. We report one rare mutation p.Met215Ile in a woman with morbid obesity. This mutation leads to changes in protein structure through the loss of hydrophobic interactions and it is predicted to be disease-causing.

Effects of three treatments on protein structure and gel properties of Perccottus glenii myofibrillar protein

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Guochuan Jiang ◽  
Lili Tian ◽  
Ruifeng Hu ◽  
Hongrui Sun ◽  
Yuan Fu ◽  
...  
Keyword(s):  
Protein Structure ◽  
Hydrophobic Interactions ◽  
Sulfhydryl Group ◽  
Myofibrillar Protein ◽  
Control Group ◽  
Perccottus Glenii ◽  
Scanning Calorimetry ◽  
Gel Properties ◽  
Protein Gels ◽  
Group Protein

Abstract In order to improve Perccottus glenii myofibrillar protein (MP) gel properties, three treatments were evaluated: ultrasonic, transglutaminase (TGase) and combined ultrasonic-transglutaminase treatments. Combined ultrasonic-transglutaminase treatment altered protein structure and gel properties most dramatically. As compared with untreated control group protein, treated protein gels possessed decreased sulfhydryl group content and increases in water holding capacity, whiteness value and hydrophobic interactions that increased gel strength value by up to 3.79 times that of untreated protein gel. Protein structural and Differential scanning calorimetry (DSC) analyses revealed that combined ultrasonic-TGase treatment increased both protein thermal denaturation temperature and UV absorbance (as compared to control and other treatment groups) that supported formation of MP gels with desirable characteristics. These results provide a theoretical basis for development of superior MP gels to promote greater utilization of this fish protein resource by the food industry.

Abstract 14729: Weight Loss Reduces Atrial Fibrillation Inducibility and Burden in Severe Obesity Induced by Either High-Fat Diet or Genetic Hyperphagia in Mice

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Eleonora Savio-Galimberti ◽  
Prince Kannankeril ◽  
David Wasserman ◽  
Dawood Darbar
Keyword(s):  
Atrial Fibrillation ◽  
Morbid Obesity ◽  
Weight Loss ◽  
High Fat Diet ◽  
Energy Homeostasis ◽  
Loss Of Function ◽  
High Fat ◽  
Knock Out ◽  
Mc4r Gene ◽  
Melanocortin 4 Receptor

Introduction: Atrial fibrillation (AF), the most common sustained arrhythmia worldwide, is associated with increased morbidity and mortality. Obesity is increasingly recognized as an important risk factor to develop AF and heart disease with a diet rich in fats leading to morbid obesity. Melanocortin-4 receptor (MC4R) gene is a critical regulator of energy homeostasis, and homozygous loss-of-function mutations cause hyperphagia and morbid obesity. Hypothesis: We hypothesized that obesity and its comorbidities can create a profibrillatory substrate for AF in high fat diet-induced obese (DIO) and MC4R knock-out (MC4R-KO) mice, and that this substrate can be reversed by weight loss. Methods: Transesophageal rapid pacing was performed using atrial burst pacing (cycle length: 50-15 ms, for 15 s) to determine AF inducibility (% of mice that develop AF) and AF burden (number of AF episodes and total AF duration/mouse) in lightly anesthesized normotensive mice (C57bl6 mice [LEAN], DIO, and MC4R-KO), with continuous ECG monitoring. Transthoracic echocardiography was performed to assess right (R) and left (L) atrial appendage (AA) sizes. Results: Atrial burst pacing induced AF in 91% of DIO and 100% of MC4R-KO vs. 50% of LEAN (P<0.01, N=8 mice/group). Compared to LEAN, both DIO and MC4R-KO exhibited greater number of inducible AF episodes (0.7±0.2 vs. 1.8±0.2 vs. 1.8±0.1, P<0.01, N=15 mice/group) with longer duration (17.9±3 vs. 196±22 vs. 244±34 s, P<0.0001, N=15 mice/group; Figure). Both DIO and MC4R-KO had greater LAA volumes as compared with LEAN (5.2±0.2 vs. 6.7±0.4 vs. 4.1±0.1 μl, P<0.01, N=8 mice/group). RAA volume was similar across groups. After 20% weight loss, both AF burden and LAA volumes were significantly reduced to those seen in LEAN (22±5 s, 4.5±0.1 μl, P<0.001, N=8 mice/group). Conclusions: High-fat diet or genetic hyperphagia-induced obesity increases LAA volume and creates a profibrillatory substrate for AF that can be reversed with weight loss.

scholarly journals A new structural model of the acid-labile subunit: pathogenetic mechanisms of short stature-causing mutations

2012 ◽  
Vol 49 (3) ◽  
pp. 213-220 ◽  
Author(s):  
Alessia David ◽  
Lawrence A Kelley ◽  
Michael J E Sternberg
Keyword(s):  
Protein Structure ◽  
Short Stature ◽  
Structure Prediction ◽  
Structural Model ◽  
Hydrophobic Interactions ◽  
Experimental Studies ◽  
Receptor Protein ◽  
Glycosylation Sites ◽  
Acid Labile Subunit ◽  
Acid Labile

The acid-labile subunit (ALS) is the main regulator of IGF1 and IGF2 bioavailability. ALS deficiency caused by mutations in the ALS (IGFALS) gene often results in mild short stature in adulthood. Little is known about the ALS structure–function relationship. A structural model built in 1999 suggested a doughnut shape, which has never been observed in the leucine-rich repeat (LRR) superfamily, to which ALS belongs. In this study, we built a new ALS structural model, analysed its glycosylation and charge distribution and studied mechanisms by which missense mutations affect protein structure. We used three structure prediction servers and integrated their results with information derived from ALS experimental studies. The ALS model was built at high confidence using Toll-like receptor protein templates and resembled a horseshoe with an extensively negatively charged concave surface. Enrichment in prolines and disulphide bonds was found at the ALS N- and C-termini. Moreover, seven N-glycosylation sites were identified and mapped. ALS mutations were predicted to affect protein structure by causing loss of hydrophobic interactions (p.Leu134Gln), alteration of the amino acid backbone (p.Leu241Pro, p.Leu172Phe and p.Leu244Phe), loss of disulphide bridges (p.Cys60Ser and p.Cys540Arg), change in structural constrains (p.Pro73Leu), creation of novel glycosylation sites (p.Asp440Asn) or alteration of LRRs (p.Asn276Ser). In conclusion, our ALS structural model was identified as a highly confident prediction by three independent methods and disagrees with the previously published ALS model. The new model allowed us to analyse the ALS core and its caps and to interpret the potential structural effects of ALS mutations.

Protein structure and function at low temperatures

1990 ◽  
Vol 326 (1237) ◽  
pp. 535-553 ◽  
Keyword(s):  
Free Energy ◽  
Protein Structure ◽  
Amino Acid ◽  
Low Temperatures ◽  
Hydrophobic Interactions ◽  
Ion Pairs ◽  
Growth Conditions ◽  
Molecular Adaptation ◽  
Catalytic Function ◽  
And Function

Proteins represent the major components in the living cell that provide the whole repertoire of constituents of cellular organization and metabolism. In the process of evolution, adaptation to extreme conditions mainly referred to temperature, pH and low water activity. With respect to life at low temperatures, effects on protein structure, protein stability and protein folding need consideration. The sequences and topologies of proteins from psychrophilic, mesophilic and thermophilic organisms are found to be highly homologous. Commonly, adaptive changes refer to multiple alterations of the amino acid sequence, which presently cannot be correlated with specific changes of structure and stability; so far it has not been possible to attribute specific increments in the free energy of stabilization to welldefined amino-acid exchanges in an unambiguous way. The stability of proteins is limited at high and low temperatures. Their expression and self-organization may be accomplished under conditions strongly deviating from optimum growth conditions. Molecular adaptation to extremes of temperature seems to be accompanied by a flattening of the temperature profile of the free energy of stabilization. In principle, the free energy of stabilization of proteins is small compared to the total molecular energy. As a consequence, molecular adaptation to extremes of physical conditions only requires marginal alterations of the intermolecular interactions and packing density. Careful statistical and structural analyses indicate that altering the number of ion pairs and hydrophobic interactions allows the flexibility of proteins to be adjusted so that full catalytic function is maintained at varying temperatures.

Evolutionary approach to protein structure prediction with hydrophobic interactions

2007 ◽  
Author(s):  
Telma Woerle de Lima ◽  
Rodrigo Antonio Faccioli ◽  
Paulo Henrique Ribeiro Gabriel ◽  
Alexandre Claudio Botazzo Delbem ◽  
Ivan Nunes da Silva
Keyword(s):  
Protein Structure ◽  
Protein Structure Prediction ◽  
Structure Prediction ◽  
Hydrophobic Interactions ◽  
Evolutionary Approach

scholarly journals Identification of p.Met215Ile mutation of the MC4R gene in a Moroccan woman with obesity

2021 ◽  
Vol 9 (11) ◽  
Author(s):  
Meriem El Fessikh ◽  
Hakim Belghiti ◽  
Zouhair Elkarhat ◽  
Hassania Guerinech ◽  
Nadia Dakka ◽  
...  
Keyword(s):  
Mc4r Gene ◽  
Moroccan Woman

scholarly journals Molecular Modelling and Dynamics Study of nsSNP in STXBP1 Gene in Early Infantile Epileptic Encephalopathy Disease

2019 ◽  
Vol 2019 ◽  
pp. 1-14
Author(s):  
Krami Al Mehdi ◽  
Benhnini Fouad ◽  
Elkarhat Zouhair ◽  
Belkady Boutaina ◽  
Naasse Yassine ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Protein Structure ◽  
High Risk ◽  
Hydrophobic Interactions ◽  
Epileptic Encephalopathy ◽  
Snare Complex ◽  
Dynamics Simulation ◽  
Conservation Analysis ◽  
The Impact ◽  
Different Levels

Early Infantile Epileptic Encephalopathy (known as Ohtahara Syndrome) is one of the most severe and earliest forms of epilepsy, characterized by early seizures onset. It affects newborns and children between two and six years old. Among the genes that have been associated with early infantile epileptic encephalopathy, the STXBP1 gene, which encodes the Syntaxin binding protein1a that is involved in SNARE complex formation, contributes to synaptic vesicles exocytosis. The aim of this study was to identify the most pathogenic polymorphisms of STXBP1 gene and determine their impact on the structure and stability of Stxbp1 protein. The high-risk nonsynonymous single nucleotide polymorphisms (nsSNPs) in the STXBP1 gene were predicted using 13 bioinformatics tools. The conservation analysis was realized by CONSURF web server. The analysis of the impact of the pathogenic SNPs on the structure of Stxbp1 protein was realized using YASARA software, and the molecular dynamics simulation was performed using GROMACS software. Out of 245 nsSNPs, we identified 11 (S42P, H103D R190W, R235G, D238E, L256P, P335S, C354Y, L365V, R406C, and G544D) as deleterious using in silico prediction tools. Conservation analysis results revealed that all these nsSNPs were located in conserved regions. The comparison of the hydrogen and hydrophobic interactions in the wild type Stxbp1 structure and its mutant forms showed that all these nsSNPs affect the protein structure on different levels. The molecular dynamics simulations revealed that the total of nsSNPs affect the protein stability, residual fluctuation, and the compaction at different levels. This study provides helpful information on high risk nsSNPs that may affect the Stxbp1 protein structure and function. Thus, these variants should be taken into consideration during the genetic screening of patients suffering from early infantile epileptic encephalopathy.

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