Structure and assembly of calcium homeostasis modulator proteins
The biological membranes of many cell types contain large-pore channels through which a wide variety of ions and metabolites permeate. Examples include connexin, innexin and pannexin, which form gap junctions and/or bona fide cell surface channels. The most recently identified large-pore channels ar...
| Main Authors: | , , , , , , , , |
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| פורמט: | Journal article |
| שפה: | English |
| יצא לאור: |
Springer
2020
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| _version_ | 1826278241094074368 |
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| author | Syrjanen, JL Michalski, K Chou, T-H Grant, T Rao, S Simorowski, N Tucker, SJ Grigorieff, N Furukawa, H |
| author_facet | Syrjanen, JL Michalski, K Chou, T-H Grant, T Rao, S Simorowski, N Tucker, SJ Grigorieff, N Furukawa, H |
| author_sort | Syrjanen, JL |
| collection | OXFORD |
| description | The biological membranes of many cell types contain large-pore channels through which a wide variety of ions and metabolites permeate. Examples include connexin, innexin and pannexin, which form gap junctions and/or bona fide cell surface channels. The most recently identified large-pore channels are the calcium homeostasis modulators (CALHMs), through which ions and ATP permeate in a voltage-dependent manner to control neuronal excitability, taste signaling and pathologies of depression and Alzheimer’s disease. Despite such critical biological roles, the structures and patterns of their oligomeric assembly remain unclear. Here, we reveal the structures of two CALHMs, chicken CALHM1 and human CALHM2, by single-particle cryo-electron microscopy (cryo-EM), which show novel assembly of the four transmembrane helices into channels of octamers and undecamers, respectively. Furthermore, molecular dynamics simulations suggest that lipids can favorably assemble into a bilayer within the larger CALHM2 pore, but not within CALHM1, demonstrating the potential correlation between pore size, lipid accommodation and channel activity. |
| first_indexed | 2024-03-06T23:41:00Z |
| format | Journal article |
| id | oxford-uuid:6f4ec7e2-0966-4a71-95f4-f45558e5db7c |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T23:41:00Z |
| publishDate | 2020 |
| publisher | Springer |
| record_format | dspace |
| spelling | oxford-uuid:6f4ec7e2-0966-4a71-95f4-f45558e5db7c2022-03-26T19:29:54ZStructure and assembly of calcium homeostasis modulator proteinsJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:6f4ec7e2-0966-4a71-95f4-f45558e5db7cEnglishSymplectic ElementsSpringer2020Syrjanen, JLMichalski, KChou, T-HGrant, TRao, SSimorowski, NTucker, SJGrigorieff, NFurukawa, HThe biological membranes of many cell types contain large-pore channels through which a wide variety of ions and metabolites permeate. Examples include connexin, innexin and pannexin, which form gap junctions and/or bona fide cell surface channels. The most recently identified large-pore channels are the calcium homeostasis modulators (CALHMs), through which ions and ATP permeate in a voltage-dependent manner to control neuronal excitability, taste signaling and pathologies of depression and Alzheimer’s disease. Despite such critical biological roles, the structures and patterns of their oligomeric assembly remain unclear. Here, we reveal the structures of two CALHMs, chicken CALHM1 and human CALHM2, by single-particle cryo-electron microscopy (cryo-EM), which show novel assembly of the four transmembrane helices into channels of octamers and undecamers, respectively. Furthermore, molecular dynamics simulations suggest that lipids can favorably assemble into a bilayer within the larger CALHM2 pore, but not within CALHM1, demonstrating the potential correlation between pore size, lipid accommodation and channel activity. |
| spellingShingle | Syrjanen, JL Michalski, K Chou, T-H Grant, T Rao, S Simorowski, N Tucker, SJ Grigorieff, N Furukawa, H Structure and assembly of calcium homeostasis modulator proteins |
| title | Structure and assembly of calcium homeostasis modulator proteins |
| title_full | Structure and assembly of calcium homeostasis modulator proteins |
| title_fullStr | Structure and assembly of calcium homeostasis modulator proteins |
| title_full_unstemmed | Structure and assembly of calcium homeostasis modulator proteins |
| title_short | Structure and assembly of calcium homeostasis modulator proteins |
| title_sort | structure and assembly of calcium homeostasis modulator proteins |
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