Low pH Overrides the Need of Calcium Ions for the Shape–Function Relationship of Calmodulin: Resolving Prevailing Debates

2014 ◽  
Vol 118 (19) ◽  
pp. 5059-5074 ◽  
Author(s):  
Kalpana Pandey ◽  
Reema R. Dhoke ◽  
Yogendra Singh Rathore ◽  
Samir K. Nath ◽  
Neha Verma ◽  
...  
Author(s):  
M. G. Monika Bai ◽  
H. Vignesh Babu ◽  
V. Lakshmi ◽  
M. Rajeswara Rao

Fluorescent porous organic polymers are a unique class of materials owing to their strong aggregation induced emission, long range exciton migration and permanent porosity, thus envisioned to possess a wide range of applications (sensing, OLEDs).


2017 ◽  
Vol 3 (8) ◽  
pp. 1700181 ◽  
Author(s):  
Nitin Saxena ◽  
Mihael Čorić ◽  
Anton Greppmair ◽  
Jan Wernecke ◽  
Mika Pflüger ◽  
...  

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Qiu Sun ◽  
Alan Perez-Rathke ◽  
Daniel M. Czajkowsky ◽  
Zhifeng Shao ◽  
Jie Liang

AbstractSingle-cell chromatin studies provide insights into how chromatin structure relates to functions of individual cells. However, balancing high-resolution and genome wide-coverage remains challenging. We describe a computational method for the reconstruction of large 3D-ensembles of single-cell (sc) chromatin conformations from population Hi-C that we apply to study embryogenesis in Drosophila. With minimal assumptions of physical properties and without adjustable parameters, our method generates large ensembles of chromatin conformations via deep-sampling. Our method identifies specific interactions, which constitute 5–6% of Hi-C frequencies, but surprisingly are sufficient to drive chromatin folding, giving rise to the observed Hi-C patterns. Modeled sc-chromatins quantify chromatin heterogeneity, revealing significant changes during embryogenesis. Furthermore, >50% of modeled sc-chromatin maintain topologically associating domains (TADs) in early embryos, when no population TADs are perceptible. Domain boundaries become fixated during development, with strong preference at binding-sites of insulator-complexes upon the midblastula transition. Overall, high-resolution 3D-ensembles of sc-chromatin conformations enable further in-depth interpretation of population Hi-C, improving understanding of the structure-function relationship of genome organization.


Biochemistry ◽  
1982 ◽  
Vol 21 (11) ◽  
pp. 2592-2600 ◽  
Author(s):  
Yee Hsiung Chen ◽  
Jang Chyi Tai ◽  
Wan Jen Huang ◽  
Ming Zong Lai ◽  
Mien Chie Hung ◽  
...  

1978 ◽  
Vol 33 (1) ◽  
pp. 235-253 ◽  
Author(s):  
J.S. Hyams ◽  
G.G. Borisy

The control of flagellar activity in the biflagellate green alga, Chlamydomonas reinhardtii was investigated by the in vitro reactivation of the isolated flagellar apparatus (the 2 flagella attached to their respective basal bodies plus accessory structures). The waveform and beat frequency of the isolated apparatus in the presence of 1 mM adenosine triphophate (ATP) were comparable to those recorded for living cells. Equimolar concentrations of adenosine diphosphate (ADP) could be substituted for ATP with little change in beat frequency and no apparent change in waveform, suggesting that the latter is converted to ATP by axonemal adenylate kinase. No reactivation occurred in adenosine monophosphate (AMP). But frequencies in cytidine, guanosine and uridine triphosphates (CTP, GTP and UTP) were approximately 10% that obtained in ATP. Reactivation was optimal over a broad pH range between pH 6.4 and pH 8.9 in both APT and ADP. Isolated flagellar apparatus could be induced to change from forward to reverse motion in vitro by manipulation of exogenous calcium ions. The 2 types of motion were directly comparable to recorded responses of living cells. Forward swimming occurred at levels of calcium below 10(−6)M, the isolated apparatus changing to backward motion above this level. Motility was inhibited at concentrations above 10(−3)M. The threshold for reversal of motion by calcium was lowered to 10(−7)M when the flagellar membranes were solubilized with detergent, indicating that the flagellar membranes are involved in the regulaion of the level of calcium within the axoneme. The reversal of motion by calcium was itself freely reversible. The relationship of these observations to the known tactic responses of Chlamydomonas is discussed.


1987 ◽  
Vol 16 (3-4) ◽  
pp. 219-226 ◽  
Author(s):  
Walter Fiers ◽  
Rudi Beyaert ◽  
Peter Brouckaert ◽  
Bart Everaerdt ◽  
Guy Haegeman ◽  
...  

2012 ◽  
Vol 49 (3) ◽  
pp. 237-248 ◽  
Author(s):  
Hui Huang ◽  
Ya-Xiong Tao

The melanocortin-4 receptor (MC4R) is a critical regulator of energy homeostasis and has emerged as a premier target for obesity treatment. Numerous mutations in transmembrane domain 6 (TM6) of MC4R resulting in functional alterations have been identified in obese patients. Several mutagenesis studies also provided some data suggesting the importance of this domain in receptor function. To gain a better understanding of the structure–function relationship of the receptor, we performed alanine-scanning mutagenesis in TM6 to determine the functions of side chains. Of the 31 residues, two were important for cell surface expression, five were indispensable for α-melanocyte-stimulating hormone (α-MSH) and β-MSH binding, and six were important for signaling in the Gs–cAMP–PKA pathway. H264A, targeted normally to the plasma membrane, was undetectable by competitive binding assay and severely defective in basal and stimulated cAMP production and ERK1/2 phosphorylation. Nine mutants had decreased basal cAMP signaling. Seven mutants were constitutively active in cAMP signaling and their basal activities could be inhibited by two MC4R inverse agonists, Ipsen 5i and ML00253764. Five mutants were also constitutively active in the MAPK pathway with enhanced basal ERK1/2 phosphorylation. In summary, our study provided comprehensive data on the structure–function relationship of the TM6 of MC4R. We identified residues that are important for cell surface expression, ligand binding, cAMP generation, and residues for maintaining the WT receptor in active conformation. We also reported constitutive activation of the MAPK pathway and biased signaling. These data will be useful for rationally designing MC4R agonists and antagonists for treatment of eating disorders.


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