Scientists See ATP Open The Door

ATP - adenosine tri-phosphate - is of fundamental importance to Biology,
because it provides energy to power cellular processes. One way cells use
ATP is to open and close membrane channels - the doors between cells and
the outside. Channel opening/closing is achieved by a change in channel
structure and new work, published in this week's issue of PLoS Biology,
describes the use of a novel technology to see directly how channel
structure changes when ATP binds.



A growing body of evidence has demonstrated that the ATP receptor-channel
family plays an important role in various disease states, but channel
structure is not fully understood. Dr. Youichi Shinozaki and colleagues
from Japanese universities studied the shape of a particular channel,
called
P2X receptor. This ATP receptor is known to have a trimeric structure and
opens its transmembrane pore when ATP binds to it. In addition to allowing
sodium and calcium ions to flow through it, P2X receptors are known to
allow larger-sized molecules through as well. This phenomenon is called as
"pore dilation." This big pore is supposed to participate in various
pathophysiologial events (e.g. a release of inflammatory cytokines, and
changes in intercellular signal transduction, et al.). It has previously
been unclear whether P2X receptor itself makes a big pore or whether other
accessory proteins are required. To address this issue, Shinozaki et al.
employed a new technique atomic force microscopy (AFM) to observe the
surface
topology of single P2X receptors.



Using AFM the research team showed that in the absence of ATP to open the
channel, P2X4Rs was circular, and that when stimulated by ATP the P2X4Rs
had
a trimeric structure. ATP-induced conformational changes in P2X4R were
successfully observed using fast-scanning AFM. The trimeric topology was
correspondent to the normal and Calcium permeable state, and the pore
dilation-like structure exhibited permeability to the large-sized
molecule.



This work will prompt further studies into how the single receptor changes
its structure to exhibit its physiological function.



Citation:

"Direct observation of ATP-induced conformational changes in single P2X4 receptors."
Shinozaki Y, Sumitomo K, Tsuda M, Koizumi S, Inoue K, et al. (2009)

PLoS Biol 7(5): e1000103. doi:10.1371/journal.pbio.1000103

Source
Plos Biology