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Comparative analysis of serotonin 5-HT receptors from X-RAY, EM, MDстатья Тезисы
- Авторы: Popinako A.V., Antonov M.Yu, Sokolova O.S., Shaitan K.V.
- Журнал: Journal of Bioenergetics and Biomembranes
- Том: 50
- Номер: 6
- Год издания: 2018
- Издательство: Springer/Plenum Publishers
- Местоположение издательства: New York, USA
- DOI: 10.1007/s10863-018-9775-7
- Аннотация: 1 Bach Institute of Biochemistry, Research Center of Biotechnology of the Russian Academy of Sciences, Leninsky Prospekt. 33, bld. 2, 119071, Moscow, Russia 2 M.K.Ammosov North-Eastern Federal University; Belinskiy str, 58, suite 312, Yakutsk, 677000, Republic of Sakha (Yakutia), Russian Federation; 3 Lomonosov Moscow State University, 1 Leninskie gory, bld 12, Moscow, 119234, Russia e-mail: popinakoav@gmail.com Ion channels form a major class of integral transmembrane proteins involved in the regulation of fundamental cellular processes [1]. The main function of ion channels is the selective movement of ions through the membranes. The importance of research of channels' structures is underscored by the identification of numerous "channelopathies", caused by ion channel mutations [2]. However, the complicated structure of eukaryotic ion channels is often a barrier to structure determination by experimental methods [3]. Thus, only one atomic X-ray structure of the pentameric ligand-dependent mammalian channel of the serotonin 5-HT3 receptor (pdb id 4PIR [4]) and one Cryo-EM structure of the serotonin 5-HT3 receptor (pdb id 6BE1 [5]) are known at the present time. The actual goal is to compare the different structures of the serotonin 5-HT3 receptors and its models constructed using the homology modeling method and molecular dynamics. The obtained models in open and closed states differ from each other in the zone of the inner vestibule. The pore radius in this region is larger in open state models than that in closed and X-ray structure. The membrane part of the X-ray structure 5-HT3 receptor and the closed state model form a zone of minimum pore radius in M2 spirals due to the oxides of the threonine hydroxyl groups. The hydrated sodium ions unable to pass through this section of the 5-HT3 receptor channel, according to the molecular dynamics data obtained in our laboratory. Thus, the X-ray structure of the 5-HT3 receptor corresponds to the closed conformation, in contradistinction to Cryo-EM structure of the serotonin 5-HT3 receptor. 1. Jegla TJ, Zmasek CM, Batalov S, Nayak SK. Evolution of the human ion channel set. Comb Chem High Throughput Screen (2009). doi: 10.2174/138620709787047957 2. Spillane, D M Kullmann, M G Hanna. Genetic neurological channelopathies: molecular genetics and clinical phenotypes. Neurogenetics (2015). http://dx.doi.org/10.1136/jnnp-2015-311233 3. Bill et al. Overcoming barriers to membrane protein structure determination. Nat Biotechnol (2011) doi:10.1038/nbt.1833. 4. Hassaine G. et al. X-ray structure of the mouse serotonin 5-HT3 receptor. Nature. (2014) 10.1038/nature13552 5. Basak S et al. Cryo-EM structure of 5-HT3A receptor in its resting conformation. Nat Commun.(2018). Doi :10.1038/s41467-018-02997-4
- Добавил в систему: Шайтан Константин Вольдемарович