The importance of cache domains in α2δ proteins and the basis for their gabapentinoid selectivity
ABSTRACTIn this hybrid review, we have first collected and reviewed available information on the structure and function of the enigmatic cache domains in α2δ proteins. These are organized into two double cache (dCache_1) domains, and they are present in all α2δ proteins. We have also included new da...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2023-12-01
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| Series: | Channels |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/19336950.2023.2167563 |
| _version_ | 1797448991758090240 |
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| author | Karen M Page Vadim M Gumerov Shehrazade Dahimene Igor B Zhulin Annette C Dolphin |
| author_facet | Karen M Page Vadim M Gumerov Shehrazade Dahimene Igor B Zhulin Annette C Dolphin |
| author_sort | Karen M Page |
| collection | DOAJ |
| description | ABSTRACTIn this hybrid review, we have first collected and reviewed available information on the structure and function of the enigmatic cache domains in α2δ proteins. These are organized into two double cache (dCache_1) domains, and they are present in all α2δ proteins. We have also included new data on the key function of these domains with respect to amino acid and gabapentinoid binding to the universal amino acid–binding pocket, which is present in α2δ-1 and α2δ-2. We have now identified the reason why α2δ-3 and α2δ-4 do not bind gabapentinoid drugs or amino acids with bulky side chains. In relation to this, we have determined that the bulky amino acids Tryptophan and Phenylalanine prevent gabapentin from inhibiting cell surface trafficking of α2δ-1. Together, these novel data shed further light on the importance of the cache domains in α2δ proteins. |
| first_indexed | 2024-03-09T14:18:25Z |
| format | Article |
| id | doaj.art-29b85d8ff155416898076adb66684e7c |
| institution | Directory Open Access Journal |
| issn | 1933-6950 1933-6969 |
| language | English |
| last_indexed | 2024-03-09T14:18:25Z |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Channels |
| spelling | doaj.art-29b85d8ff155416898076adb66684e7c2023-11-28T18:09:44ZengTaylor & Francis GroupChannels1933-69501933-69692023-12-0117110.1080/19336950.2023.2167563The importance of cache domains in α2δ proteins and the basis for their gabapentinoid selectivityKaren M Page0Vadim M Gumerov1Shehrazade Dahimene2Igor B Zhulin3Annette C Dolphin4Department of Neuroscience, Physiology and Pharmacology, University College London, London, UKDepartment of Microbiology and Translational Data Analytics Institute, The Ohio State University, Columbus, OH, USADepartment of Neuroscience, Physiology and Pharmacology, University College London, London, UKDepartment of Microbiology and Translational Data Analytics Institute, The Ohio State University, Columbus, OH, USADepartment of Neuroscience, Physiology and Pharmacology, University College London, London, UKABSTRACTIn this hybrid review, we have first collected and reviewed available information on the structure and function of the enigmatic cache domains in α2δ proteins. These are organized into two double cache (dCache_1) domains, and they are present in all α2δ proteins. We have also included new data on the key function of these domains with respect to amino acid and gabapentinoid binding to the universal amino acid–binding pocket, which is present in α2δ-1 and α2δ-2. We have now identified the reason why α2δ-3 and α2δ-4 do not bind gabapentinoid drugs or amino acids with bulky side chains. In relation to this, we have determined that the bulky amino acids Tryptophan and Phenylalanine prevent gabapentin from inhibiting cell surface trafficking of α2δ-1. Together, these novel data shed further light on the importance of the cache domains in α2δ proteins.https://www.tandfonline.com/doi/10.1080/19336950.2023.2167563Voltage-gated calcium channelgabapentinoidcache domainamino acidα2δ protein |
| spellingShingle | Karen M Page Vadim M Gumerov Shehrazade Dahimene Igor B Zhulin Annette C Dolphin The importance of cache domains in α2δ proteins and the basis for their gabapentinoid selectivity Channels Voltage-gated calcium channel gabapentinoid cache domain amino acid α2δ protein |
| title | The importance of cache domains in α2δ proteins and the basis for their gabapentinoid selectivity |
| title_full | The importance of cache domains in α2δ proteins and the basis for their gabapentinoid selectivity |
| title_fullStr | The importance of cache domains in α2δ proteins and the basis for their gabapentinoid selectivity |
| title_full_unstemmed | The importance of cache domains in α2δ proteins and the basis for their gabapentinoid selectivity |
| title_short | The importance of cache domains in α2δ proteins and the basis for their gabapentinoid selectivity |
| title_sort | importance of cache domains in α2δ proteins and the basis for their gabapentinoid selectivity |
| topic | Voltage-gated calcium channel gabapentinoid cache domain amino acid α2δ protein |
| url | https://www.tandfonline.com/doi/10.1080/19336950.2023.2167563 |
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