Functional Characterization of a P2X Receptor from Schistosoma mansoni

Agboh, Kelvin; Webb, Tania E.; Evans, Richard J.; Ennion, Steven J.

doi:10.1074/jbc.m408203200

Cited by 97 publications

(104 citation statements)

References 40 publications

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“…The evolutionary origin of P2X receptors is still unclear; however, ancestral organisms diverging as far as 1 billion years ago have a single P2X receptor that has pharmacological and biophysical properties that resemble those of the seven P2X subunits in vertebrates [14] [17] [18] [54] [55]. As we have shown in this work, there is a high conservation of the gene structure among P2X receptors in the different organisms analyzed, even in the distant species of fish and reptile.…”

Section: Discussionmentioning

confidence: 59%

Genomic Organization of Purinergic P2X Receptors

Loera-Valencia¹,

Jaramillo-Polanco²,

Liñán-Rico³

et al. 2015

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Purinergic P2X receptors are a family of ligand-gated cationic channels activated by extracellular ATP. P2X subunit protein sequences are highly conserved between vertebrate species. However, they can generate a great diversity of coding splicing variants to fulfill several roles in mammalian physiology. Despite intensive research in P2X expression in both central and peripheral nervous system, there is little information about their homology, genomic structure and other key features that can help to develop selective drugs or regulatory strategies of pharmacological value which are lacking today. In order to obtain clues on mammalian P2X diversity, we have performed a bioinformatics analysis of the coding regions and introns of the seven P2X subunits present in human, simian, dog, mouse, rat and zebrafish. Here we report the arrangements of exon and intron sequences, considering its number, size, phase and placement; proposing some ideas about the gain and loss of exons and retention of introns. Taken together, these evidences show traits that can be used to gain insight into the evolutionary history of vertebrate P2X receptors and better understand the diversity of subunits coding the purinergic signaling in mammals.

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Section: Discussionmentioning

confidence: 59%

Genomic Organization of Purinergic P2X Receptors

Loera-Valencia¹,

Jaramillo-Polanco²,

Liñán-Rico³

et al. 2015

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“…However, the distance between Thr-336 residues of open channels, if they are at the gate as our data and the model suggests (see below and Fig. 7), is expected to be greater than 8 Å, which is the minimal open pore diameter based on ion replacement studies (11,61,(65)(66)(67)(68)(69). Thus, we believe Cd 2ϩ is not tightly bound at T336C and most other TM2 hits because the number of available cysteines and the distance between them is not optimal for coordination.…”

Section: ϩmentioning

confidence: 99%

Gated Access to the Pore of a P2X Receptor

Kracun

Chaptal

Abramson

et al. 2010

Journal of Biological Chemistry

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P2X receptors (P2X1-P2X7) are cell surface cation channels that transition from closed to open states upon binding ATP. They represent a physiologically and medically important (1), as well as a structurally distinct family of ligand-gated ion channels that are quite different to Cys-loop and ionotropic glutamate receptors (2-5). P2X receptors are found in many species from several phyla, implying important roles in diverse life forms (6, 7). A key goal is to understand how P2X receptors operate at the chemical level.The first P2X receptor genes were cloned in 1994 (8, 9) leading to important progress over the last decade in understanding how P2X receptors function (10, 11) using biophysical and biochemical approaches. P2X subunits are thus known to possess intracellular N and C termini and two transmembrane (TM) 2 segments separated by a large extracellular loop (12-14). The trimeric architecture of P2X receptors is also well established based on subunit concatemers, blue-native PAGE, and atomic force microscopy experiments (15-18). It is also well established that the P2X pore is lined by TM2 (19 -22), with TM1 making little contribution to ion flow (23, 24). Moreover, careful studies of permeation and selectivity have suggested that the same area of TM2 is responsible for both ion selection and channel opening (25-31). Mutational approaches have shed light on the extracellular domain of P2X receptors, including how the ATP binding pocket may form (32), how the 10 conserved cysteines contribute to the fold of the protein (33, 34), and how cations such as Zn 2ϩ profoundly affect receptor function (35)(36)(37)(38). Finally, meticulous analysis of voltage-jump relaxations for ATP-evoked currents combined with mutagenesis has suggested that TM2 may display hinge-like flexibility (39, 40), and recently the P2X4 receptor open pore has been imaged with fast scanning atomic force microscopy (41). Most of these past studies were conducted on rat P2X2 (rP2X2) receptors and have provided a basis to explore P2X receptor pores and the gating process.In 2009, the field was immeasurably advanced by the landmark achievement and report of a crystal structure of the zebrafish (zf) P2X4.1 receptor in the closed state (42). The P2X receptor topology was similar to that of acid-sensing ion channels (42, 43), a possibility that had been raised by earlier modeling studies (44). However, it is important to note that the extracellular domains of P2X and acid-sensing ion channels are distinct with little sequence or structural homology, whereas the pore domains share similar architectures (43). The availability of direct structural information for P2X receptors substantiated most of the aforementioned mutational studies and for the first time provided a framework to understand their atomic origins (5). Of most relevance here, it directly revealed that the P2X pore was indeed formed by TM2 ␣-helices arranged around a 3-fold molecular axis of symmetry. These were arranged ϳ45°to the membrane normal and crossed about halfway along their l...

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“…From then, P2X receptors have been found in several vertebrates and invertebrate species [3,4]. Specially, mammalian species have seven P2X subtypes which are named from P2X1 to P2X7.…”

Section: Introductionmentioning

confidence: 99%

Comparative study of the P2X gene family in animals and plants

Hou

Cao

2016

Purinergic Signalling

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P2X receptors are ligand-gated ion channels that can bind with the adenosine triphosphate (ATP) and have diverse functional roles in neuropathic pain, inflammation, special sense, and so on. In this study, 180 putative P2X genes, including 176 members in 32 animal species and 4 members in 3 species of lower plants, were identified. These genes were divided into 13 groups, including 7 groups in vertebrates and 6 groups in invertebrates and lower plants, through phylogenetic analysis. Their gene organization and motif composition are conserved in most predicted P2X members, while groupspecific features were also found. Moreover, synteny relationships of the putative P2X genes in vertebrates are conserved while simultaneously experiencing a series of gene insertion, inversion, and transposition. Recombination signals were detected in almost all of the vertebrates and invertebrates, suggesting that intragenic recombination may play a significant role in the evolution of P2X genes. Selection analysis also identified some positively selected sites that acted on the evolution of most of the predicted P2X proteins. The phenomenon of alternative splicing occurred commonly in the putative P2X genes of vertebrates. This article explored in depth the evolutional relationship among different subtypes of P2X genes in animal and plants and might serve as a solid foundation for deciphering their functions in further studies.

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Functional Characterization of a P2X Receptor from Schistosoma mansoni

Cited by 97 publications

References 40 publications

Genomic Organization of Purinergic P2X Receptors

Genomic Organization of Purinergic P2X Receptors

Gated Access to the Pore of a P2X Receptor

Comparative study of the P2X gene family in animals and plants

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