TY - JOUR
T1 - Structure versus function
T2 - Are new conformations of pannexin 1 yet to be resolved?
AU - Mim, Carsten
AU - Perkins, Guy
AU - Dahl, Gerhard
N1 - Funding Information:
Crina M. Nimigean served as editor. We thank Dr. Ken Muller for critically reading an early version of the manuscript. This work was supported by a grant from the National Institutes of Health (R56HL136291 to G. Dahl and G. Perkins). The authors declare no competing financial interests. Author contributions: C. Mim, G. Perkins, and G. Dahl jointly conceived, wrote, and edited the manuscript.
Publisher Copyright:
© 2021 Mim et al.
PY - 2021/5/3
Y1 - 2021/5/3
N2 - Pannexin 1 (Panx1) plays a decisive role in multiple physiological and pathological settings, including oxygen delivery to tissues, mucociliary clearance in airways, sepsis, neuropathic pain, and epilepsy. It is widely accepted that Panx1 exerts its role in the context of purinergic signaling by providing a transmembrane pathway for ATP. However, under certain conditions, Panx1 can also act as a highly selective membrane channel for chloride ions without ATP permeability. A recent flurry of publications has provided structural information about the Panx1 channel. However, while these structures are consistent with a chloride selective channel, none show a conformation with strong support for the ATP release function of Panx1. In this Viewpoint, we critically assess the existing evidence for the function and structure of the Panx1 channel and conclude that the structure corresponding to the ATP permeation pathway is yet to be determined. We also list a set of additional topics needing attention and propose ways to attain the large-pore, ATP-permeable conformation of the Panx1 channel.
AB - Pannexin 1 (Panx1) plays a decisive role in multiple physiological and pathological settings, including oxygen delivery to tissues, mucociliary clearance in airways, sepsis, neuropathic pain, and epilepsy. It is widely accepted that Panx1 exerts its role in the context of purinergic signaling by providing a transmembrane pathway for ATP. However, under certain conditions, Panx1 can also act as a highly selective membrane channel for chloride ions without ATP permeability. A recent flurry of publications has provided structural information about the Panx1 channel. However, while these structures are consistent with a chloride selective channel, none show a conformation with strong support for the ATP release function of Panx1. In this Viewpoint, we critically assess the existing evidence for the function and structure of the Panx1 channel and conclude that the structure corresponding to the ATP permeation pathway is yet to be determined. We also list a set of additional topics needing attention and propose ways to attain the large-pore, ATP-permeable conformation of the Panx1 channel.
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U2 - 10.1085/jgp.202012754
DO - 10.1085/jgp.202012754
M3 - Article
C2 - 33835130
AN - SCOPUS:85104209639
VL - 153
JO - Journal of General Physiology
JF - Journal of General Physiology
SN - 0022-1295
IS - 5
M1 - e202012754
ER -