The vanilloid transient receptor potential channel TRPV3 is a putative molecular thermosensor widely considered to be involved in cutaneous sensation, skin homeostasis, nociception, and pruritus. Repeated stimulation of TRPV3 by high temperatures above 50 °C progressively increases its responses and shifts the activation threshold to physiological temperatures. This use-dependence does not occur in the related heat-sensitive TRPV1 channel in which responses decrease, and the activation threshold is retained above 40 °C during activations. By combining structure-based mutagenesis, electrophysiology, and molecular modeling, we showed that chimeric replacement of the residues from the TRPV3 cytoplasmic inter-subunit interface (N251-E257) with the homologous residues of TRPV1 resulted in channels that, similarly to TRPV1, exhibited a lowered thermal threshold, were sensitized, and failed to close completely after intense stimulation. Crosslinking of this interface by the engineered disulfide bridge between substituted cysteines F259C and V385C (or, to a lesser extent, Y382C) locked the channel in an open state. On the other hand, mutation of a single residue within this region (E736) resulted in heat resistant channels. We propose that alterations in the cytoplasmic inter-subunit interface produce shifts in the channel gating equilibrium and that this domain is critical for the use-dependence of the heat sensitivity of TRPV3.

10.3390/ijms20163990

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Computer Simulation of the Exciton Transfer in the Coupled Ring Antenna Subunits of Bacteria Photosynthetic Systems

The Journal of Physical Chemistry B (1999)

Pavel Heřman Ivan Barvı́k

A common accepted feature of the purple bacteria antenna systems seems to be a ring structure of their subunits LH2 and LH1. We concentrate our investigation on a delivery time of the energy through the subunits LH2 and LH1 of the antenna system to the reaction center. We are dealing with a model system consisting of one ring LH2 and one ring LH1. We have used structure data from Rhodopseudomonas acidophila. We investigate the exciton transfer inside and between LH2 and LH1 rings in the presence of the interaction with a bath. One can expect the incoherent (hopping) regime of the exciton transfer among the LH2 and LH1 rings. The exciton transfer inside the rings LH2 and LH1 is treated in a quasicoherent regime. One is therefore forced to deal with the time development of the full exciton density matrix of the exciton to take into account phase relations given by off-diagonal elements, completing in such a way information given by the site occupation probabilities Pm(t), diagonal elements of the exciton density matrix. Time dependence of the exciton density matrix is governed by dynamic equations which form an extension of the stochastic Liouville equation method with a Haken−Strobl−Reineker parametrization. Some known shortcomings of the original HSR−SLE treatment are removed in our model: (a) we replace a classical stochastic field by a quantum field and (b) we introduce a new parameter A to provide a correct imbalance among the extended states at finite temperatures for long times due to energy relaxation. We discuss the influence of a local energy and a transfer integral heterogeneity, distance, and orientation dependence of the transfer rates between rings, relaxation, etc., on the energy delivery time.

Purple bacteria

Matrix (chemical analysis)

Biexciton

Parametrization (atmospheric modeling)

10.1021/jp9908855

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Tuning the hybridization properties of modified oligonucleotides: from flexible to conformationally constrained phosphonate internucleotide linkages

Organic & Biomolecular Chemistry (2016)

Ondřej Páv Ivan Barvı́k Radek Liboska Magdalena Petrová Ondřej Šimák

The concept of conformational restriction leading to the preorganization of modified strands has proven to be successful and has afforded nucleic acid analogues with many interesting properties suitable for various biochemical applications. We utilized this concept to prepare a set of constrained oligonucleotides derived from 1,4-dioxane and 1,3-dioxolane-locked nucleoside phosphonates and evaluated their hybridization affinities towards their complementary RNA strands. With an increase of ΔTm per modification up to +5.2 °C, the hybridization experiments revealed the (S)-2',3'-O-phosphonomethylidene internucleotide linkage as one of the most Tm-increasing modifications reported to date. Moreover, we introduced a novel prediction tool for the pre-selection of potentially interesting chemical modifications of oligonucleotides.

Phosphonate

10.1039/c6ob02571d

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CapZyme-Seq Comprehensively Defines Promoter-Sequence Determinants for RNA 5′ Capping with NAD+

Molecular Cell (2018)

Irina O. Vvedenskaya Jeremy G. Bird Yuanchao Zhang Yu Zhang Xinfu Jiao

Sequence (biology)

10.1016/j.molcel.2018.03.014

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Citations (71)

Recognition of 2′,5′-linked oligoadenylates by human ribonuclease L: molecular dynamics study