Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/30776
Title: Predictions suggesting a participation of beta-sheet configuration in the M2 domain of the P2X(7) receptor: a novel conformation?
Authors: Teixeira, Pedro Celso Nogueira
Souza, Cristina Alves Magalhães de
Freitas, Mônica Santos de
Foguel, Débora
Caffarena, Ernesto Raul
Alves, Luiz Anastacio
Affilliation: Fundação Mokiti Okada. Centro de Pesquisa. Ipeúna, SP, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Comunicação Celular. Rio de Janeiro, RJ. Brasil.
Universidade Federal do Rio de Janeiro. Instituto de Bioquímica Médica. Centro Nacional de Ressonância Magné tica Nuclear Jiri Jonas. Programa de Biologia Estrutural. Rio de Janeiro, RJ, Brasil.
Universidade Federal do Rio de Janeiro. Instituto de Bioquímica Médica. Centro Nacional de Ressonância Magné tica Nuclear Jiri Jonas. Programa de Biologia Estrutural. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Programa Computação Científica. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Comunicação Celular. Rio de Janeiro, RJ. Brasil.
Abstract: Scanning experiments have shown that the putative TM2 domain of the P2X(7) receptor (P2X(7)R) lines the ionic pore. However, none has identified an alpha-helix structure, the paradigmatic secondary structure of ion channels in mammalian cells. In addition, some researchers have suggested a beta-sheet conformation in the TM2 domain of P2X(2). These data led us to investigate a new architecture within the P2X receptor family. P2X(7)R is considered an intriguing receptor because its activation induces nonselective large pore formation, in contrast to the majority of other ionic channel proteins in mammals. This receptor has two states: a low-conductance channel (approximately 10 pS) and a large pore (> 400 pS). To our knowledge, one fundamental question remains unanswered: Are the P2X(7)R channel and the pore itself the same entity or are they different structures? There are no structural data to help solve this question. Thus, we investigated the hydrophobic M2 domain with the aim of predicting the fitted position and the secondary structure of the TM2 segment from human P2X(7)R (hP2X(7)R). We provide evidence for a beta-sheet conformation, using bioinformatics algorithms and molecular-dynamics simulation in conjunction with circular dichroism in different environments and Fourier transform infrared spectroscopy. In summary, our study suggests the possibility that a segment composed of residues from part of the M2 domain and part of the putative TM2 segment of P2X(7)R is partially folded in a beta-sheet conformation, and may play an important role in channel/pore formation associated with P2X(7)R activation. It is important to note that most nonselective large pores have a transmembrane beta-sheet conformation. Thus, this study may lead to a paradigmatic change in the P2X(7)R field and/or raise new questions about this issue.
Keywords: P2X7R
M2 Domain
b-Sheet Configuration
ATP-gated ion channels
keywords: receptor P2X7
domínio M2
Configuração de b-Sheet
Issue Date: 2009
Publisher: Biophysical Society
Citation: TEIXEIRA, Pedro Celso Nogueira; et al. Predictions Suggesting a Participation of b-Sheet Configuration in the M2 Domain of the P2X7 Receptor: A Novel Conformation?. Biophysial Journal, v.96, p.951-963, Feb. 2009.
DOI: 10.1016/j.bpj.2008.10.043
ISSN: 0006-3495
Copyright: restricted access
Appears in Collections:IOC - Artigos de Periódicos

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