Počet záznamů: 1

Regulation of the transient receptor potential channel TRPA1 by its N-terminal ankyrin repeat domain

SYSNO ASEP	0381621
Druh ASEP	J - Článek v odborném periodiku
Zařazení RIV	J - Článek v odborném periodiku
Poddruh J	Článek ve WOS
Název	Regulation of the transient receptor potential channel TRPA1 by its N-terminal ankyrin repeat domain
Tvůrce(i)	Zayats, Vasilina (UEK-B)_{RID, SAI, ORCID} Samad, Abdul (UEK-B) Minofar, Babak (UEK-B)_RID Roelofs, K. E. (US) Stockner, T. (AT) Ettrich, Rüdiger (UEK-B)_{RID, ORCID, SAI}
Celkový počet autorů	6
Zdroj.dok.	Journal of Molecular Modeling. - : Springer - ISSN 1610-2940 Roč. 19, č. 11 (2012), s. 4689-4700
Poč.str.	12 s.
Jazyk dok.	eng - angličtina
Země vyd.	CZ - Česká republika
Klíč. slova	ankyrin repeat ; EF-hand ; familial episodic pain syndrom ; TRPA1
Vědní obor RIV	CE - Biochemie
CEP	GAP207/10/1934 GA ČR - Grantová agentura ČR
CEZ	AV0Z60870520 - UEK-B (2005-2011)
UT WOS	000326193200009
EID SCOPUS	84888289833
DOI	10.1007/s00894-012-1505-1
Anotace	The transient receptor potential channel A1 (TRPA1) is unique among ion channels of higher vertebrates in that it harbors a large ankyrin repeat domain. The TRPA1 channel is expressed in the inner ear and in nociceptive neurons. It is involved in hearing as well as in the perception of pungent and irritant chemicals. The ankyrin repeat domain has special mechanical properties, which allows it to function as a soft spring that can be extended over a large range while maintaining structural integrity. A calcium-binding site has been experimentally identified within the ankyrin repeats. We built a model of the N-terminal 17 ankyrin repeat structure, including the calcium-binding EF-hand. In our simulations we find the calcium-bound state to be rigid as compared to the calcium-free state. While the end-to-end distance can change by almost 50% in the apo form, these fluctuations are strongly reduced by calcium binding. This increase in stiffness that constraints the end-to-end distance in the holo form is predicted to affect the force acting on the gate of the TRPA1 channel, thereby changing its open probability. Simulations of the transmembrane domain of TRPA1 show that residue N855, which has been associated with familial episodic pain syndrome, forms a strong link between the S4-S5 connecting helix and S1, thereby creating a direct force link between the N-terminus and the gate. The N855S mutation weakens this interaction, thereby reducing the communication between the N-terminus and the transmembrane part of TRPA1.
Pracoviště	Ústav výzkumu globální změny
Kontakt	Nikola Šviková, svikova.n@czechglobe.cz, Tel.: 511 192 268
Rok sběru	2014

Počet záznamů: 1