The His-Gly motif of acid-sensing ion channels resides in a reentrant ‘loop’ implicated in gating and ion selectivity
Acid-sensing ion channels (ASICs) are proton-gated members of the epithelial sodium channel/degenerin (ENaC/DEG) superfamily of ion channels and are expressed throughout the central and peripheral nervous systems. The homotrimeric splice variant ASIC1a has been implicated in nociception, fear memory...
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2020-06-01
|
| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/56527 |
| _version_ | 1818028561801412608 |
|---|---|
| author | Nate Yoder Eric Gouaux |
| author_facet | Nate Yoder Eric Gouaux |
| author_sort | Nate Yoder |
| collection | DOAJ |
| description | Acid-sensing ion channels (ASICs) are proton-gated members of the epithelial sodium channel/degenerin (ENaC/DEG) superfamily of ion channels and are expressed throughout the central and peripheral nervous systems. The homotrimeric splice variant ASIC1a has been implicated in nociception, fear memory, mood disorders and ischemia. Here, we extract full-length chicken ASIC1 (cASIC1) from cell membranes using styrene maleic acid (SMA) copolymer, elucidating structures of ASIC1 channels in both high pH resting and low pH desensitized conformations by single-particle cryo-electron microscopy (cryo-EM). The structures of resting and desensitized channels reveal a reentrant loop at the amino terminus of ASIC1 that includes the highly conserved ‘His-Gly’ (HG) motif. The reentrant loop lines the lower ion permeation pathway and buttresses the ‘Gly-Ala-Ser’ (GAS) constriction, thus providing a structural explanation for the role of the His-Gly dipeptide in the structure and function of ASICs. |
| first_indexed | 2024-12-10T05:05:45Z |
| format | Article |
| id | doaj.art-03db86394715445caab0cb76e8c5543e |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-12-10T05:05:45Z |
| publishDate | 2020-06-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-03db86394715445caab0cb76e8c5543e2022-12-22T02:01:15ZengeLife Sciences Publications LtdeLife2050-084X2020-06-01910.7554/eLife.56527The His-Gly motif of acid-sensing ion channels resides in a reentrant ‘loop’ implicated in gating and ion selectivityNate Yoder0https://orcid.org/0000-0002-9017-0673Eric Gouaux1https://orcid.org/0000-0002-8549-2360Vollum Institute, Oregon Health & Science University, Portland, United StatesVollum Institute, Oregon Health & Science University, Portland, United States; Howard Hughes Medical Institute, Oregon Health & Science University, Portland, United StatesAcid-sensing ion channels (ASICs) are proton-gated members of the epithelial sodium channel/degenerin (ENaC/DEG) superfamily of ion channels and are expressed throughout the central and peripheral nervous systems. The homotrimeric splice variant ASIC1a has been implicated in nociception, fear memory, mood disorders and ischemia. Here, we extract full-length chicken ASIC1 (cASIC1) from cell membranes using styrene maleic acid (SMA) copolymer, elucidating structures of ASIC1 channels in both high pH resting and low pH desensitized conformations by single-particle cryo-electron microscopy (cryo-EM). The structures of resting and desensitized channels reveal a reentrant loop at the amino terminus of ASIC1 that includes the highly conserved ‘His-Gly’ (HG) motif. The reentrant loop lines the lower ion permeation pathway and buttresses the ‘Gly-Ala-Ser’ (GAS) constriction, thus providing a structural explanation for the role of the His-Gly dipeptide in the structure and function of ASICs.https://elifesciences.org/articles/56527ASICacid-sensing ion channelproton-gated ion channelligand-gated ion channelENaCepithelial sodium channel |
| spellingShingle | Nate Yoder Eric Gouaux The His-Gly motif of acid-sensing ion channels resides in a reentrant ‘loop’ implicated in gating and ion selectivity eLife ASIC acid-sensing ion channel proton-gated ion channel ligand-gated ion channel ENaC epithelial sodium channel |
| title | The His-Gly motif of acid-sensing ion channels resides in a reentrant ‘loop’ implicated in gating and ion selectivity |
| title_full | The His-Gly motif of acid-sensing ion channels resides in a reentrant ‘loop’ implicated in gating and ion selectivity |
| title_fullStr | The His-Gly motif of acid-sensing ion channels resides in a reentrant ‘loop’ implicated in gating and ion selectivity |
| title_full_unstemmed | The His-Gly motif of acid-sensing ion channels resides in a reentrant ‘loop’ implicated in gating and ion selectivity |
| title_short | The His-Gly motif of acid-sensing ion channels resides in a reentrant ‘loop’ implicated in gating and ion selectivity |
| title_sort | his gly motif of acid sensing ion channels resides in a reentrant loop implicated in gating and ion selectivity |
| topic | ASIC acid-sensing ion channel proton-gated ion channel ligand-gated ion channel ENaC epithelial sodium channel |
| url | https://elifesciences.org/articles/56527 |
| work_keys_str_mv | AT nateyoder thehisglymotifofacidsensingionchannelsresidesinareentrantloopimplicatedingatingandionselectivity AT ericgouaux thehisglymotifofacidsensingionchannelsresidesinareentrantloopimplicatedingatingandionselectivity AT nateyoder hisglymotifofacidsensingionchannelsresidesinareentrantloopimplicatedingatingandionselectivity AT ericgouaux hisglymotifofacidsensingionchannelsresidesinareentrantloopimplicatedingatingandionselectivity |