bioRxiv ScienceSearch

bioRxiv · 10.1101/018580

Pluripotency Conversion of Gene Studied from Quantum Folding Theory

Abstract

The chemically and physically induced pluripotency in a stem cell is studied from the point of quantum transition between differentiation and pluripotency states in genes. The quantum folding theory of a macromolecule is briefly reviewed. The relation of protein folding rate with the number N of torsion modes participating in the quantum transition (coherence degree) is discussed and a simple statistical relationship is obtained. As a unifying approach to conformational quantum transition the folding rate formula can be generalized from protein to nucleic acid. It is found that the formula of folding rate versus N well fits RNA folding data. Then the quantum folding theory is applied to study the pluripotency conversion in stem cell. We proved that the acquisition of pluripotency is essentially a quantum-stochastic event of small-probability through the comparison of the rate with protein folding. Due to the large coherence degree of DNA and the uphill nature of torsion transition the pluripotency-acquisition rate should be small. By establishing the reaction network of the conformational change of the pluripotency genes the characteristic time of the chemical reprogramming is calculated and the result is consistent with experiments. The dependence of the transition rate on physical factors such as temperature, PH value and the volume and shape of the coherent domain of the gene is analyzed from the rate equation. Based on these studies an approach to the physically induced pluripotency with higher rate is proposed.

Explore related subjects

Keep this discovery

BibTeXRIS

Liaofu Luo. 2015-04-26. Pluripotency Conversion of Gene Studied from Quantum Folding Theory. https://doi.org/10.1101/018580

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

TatA complexes exhibit a marked change in organisation in response to expression of the TatBC complex

The twin arginine translocation (Tat) system is an integral membrane protein complex that accomplishes the remarkable feat of transporting large, fully-folded polypeptides across the inner membrane of bacteria, into the periplasm. In Escherichia coli Tat is comprised of three membrane proteins: TatA, TatB and TatC. How these proteins arrange themselves in the inner membrane to permit passage of Tat substrates, whilst maintaining membrane integrity, is still poorly understood. TatA is the most abundant component of this complex and facilitates assembly of the transport mechanism. We have utilised immunogold labelling in combination with array tomography to gain insight into the localisation and distribution of the TatA protein in E. coli cells. We show that TatA exhibits a uniform distribution throughout the inner membrane of E. coli and that altering the expression of TatBC shows a previously uncharacterised distribution of TatA in the inner membrane. Array tomography was used to provide our first insight into this altered distribution of TatA in 3D space, revealing that this protein forms linear clusters in the inner membrane of E. coli upon increased expression of TatBC. This is the first indication that TatA organisation in the inner membrane alters in response to changes in Tat subunit stoichiometry.\n\nSummary statementThe volumetric electron-microscopy technique, array tomography, revealed a novel distribution of TatA protein (from the twin arginine translocase complex), in Escherichia coli.

Biophysics

A unified coarse-grained theory of bacterial physiology explains the relationship between cell size, growth rate and proteome composition under various growth limitations

Universal observations in Biology are sometimes described as "laws". In E. coli, experimental studies performed over the past six decades have revealed major growth laws relating ribosomal mass fraction and cell size to the growth rate. Because they formalize complex emerging principles in biology, growth laws have been instrumental in shaping our understanding of bacterial physiology. Here, we discovered a novel size law that connects cell size to the inverse of the metabolic proteome mass fraction and the active fraction of ribosomes. We used a simple whole-cell coarse-grained model of cell physiology that combines the proteome allocation theory and the structural model of cell division. The model captures all available experimental data connecting the cell proteome composition, ribosome activity, division size and growth rate in response to nutrient quality, antibiotic treatment and increased protein burden. Finally, a stochastic extension of the model explains non-trivial correlations observed in single cell experiments including the adder principle. This work provides a simple and robust theoretical framework for studying the fundamental principles of cell size determination in unicellular organisms.

Biophysics

Identification of a Zika NS2B-NS3pro pocket susceptible to allosteric inhibition by small molecules including qucertin rich in edible plants

It has been recently estimated that one-third of the world population will be infected by Zika virus, but unfortunately so far there is no vaccine or medicine available. In particular, the special concern on the vaccine treatment to Zika and Dengue arising from antibody-dependent enhancement strongly emphasizes the irreplaceable role of its NS2B-NS3 protease (NS2B-NS3pro) as a target for anti-Zika drug discovery/design due to its absolutely-essential role in viral replication. Very recently we identified two small molecules inhibit Zika NS2B-NS3pro in non-competitive mode, with Ki values of 0.57 and 2.02 {micro}M respective for p-Nitrophenyl-p-guanidino benzoate and qucertin. Here, by molecular docking, we show that although one is designed compound while another is a natural product, both molecules bind to the same pocket on the back of the substrate-binding pocket of Zika NS2B-NS3pro. As the two inhibitors fundamentally differ from cn-716, the only known peptidomimetic boronic acid inhibitor in both structure scaffolds and inhibitory modes, our discovery might open up a new avenue for the future development of allosteric inhibitors, which is highly demanded to achieve therapeutic inhibition of flaviviral NS2B-NS3pro complexes. Furthermore, as qucertin is abundant in many vegetables and fruits such caper, lovage, tea and red onion, our results should benefit the public to immediately fight Zika virus.

Biophysics