Pursuing High-Resolution Structures of Nicotinic Acetylcholine Receptors: Lessons Learned from Five Decades
Since their discovery, nicotinic acetylcholine receptors (nAChRs) have been extensively studied to understand their function, as well as the consequence of alterations leading to disease states. Importantly, these receptors represent pharmacological targets to treat a number of neurological and neur...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-09-01
|
| Series: | Molecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1420-3049/26/19/5753 |
| _version_ | 1797515989661777920 |
|---|---|
| author | Manuel Delgado-Vélez Orestes Quesada Juan C. Villalobos-Santos Rafael Maldonado-Hernández Guillermo Asmar-Rovira Raymond C. Stevens José Antonio Lasalde-Dominicci |
| author_facet | Manuel Delgado-Vélez Orestes Quesada Juan C. Villalobos-Santos Rafael Maldonado-Hernández Guillermo Asmar-Rovira Raymond C. Stevens José Antonio Lasalde-Dominicci |
| author_sort | Manuel Delgado-Vélez |
| collection | DOAJ |
| description | Since their discovery, nicotinic acetylcholine receptors (nAChRs) have been extensively studied to understand their function, as well as the consequence of alterations leading to disease states. Importantly, these receptors represent pharmacological targets to treat a number of neurological and neurodegenerative disorders. Nevertheless, their therapeutic value has been limited by the absence of high-resolution structures that allow for the design of more specific and effective drugs. This article offers a comprehensive review of five decades of research pursuing high-resolution structures of nAChRs. We provide a historical perspective, from initial structural studies to the most recent X-ray and cryogenic electron microscopy (Cryo-EM) nAChR structures. We also discuss the most relevant structural features that emerged from these studies, as well as perspectives in the field. |
| first_indexed | 2024-03-10T06:54:58Z |
| format | Article |
| id | doaj.art-62a51a61ae6f4d23bdcad2ffac30df5b |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T06:54:58Z |
| publishDate | 2021-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-62a51a61ae6f4d23bdcad2ffac30df5b2023-11-22T16:32:07ZengMDPI AGMolecules1420-30492021-09-012619575310.3390/molecules26195753Pursuing High-Resolution Structures of Nicotinic Acetylcholine Receptors: Lessons Learned from Five DecadesManuel Delgado-Vélez0Orestes Quesada1Juan C. Villalobos-Santos2Rafael Maldonado-Hernández3Guillermo Asmar-Rovira4Raymond C. Stevens5José Antonio Lasalde-Dominicci6Department of Biology, Rio Piedras Campus, University of Puerto Rico, San Juan 00931, Puerto RicoClinical Bioreagent Center, Molecular Sciences Research Center, University of Puerto Rico, San Juan 00926, Puerto RicoDepartment of Biology, Rio Piedras Campus, University of Puerto Rico, San Juan 00931, Puerto RicoClinical Bioreagent Center, Molecular Sciences Research Center, University of Puerto Rico, San Juan 00926, Puerto RicoIndependent Researcher, Ambler, PA 19002, USAMichelson Center for Convergent Bioscience, Department of Biological Sciences, Bridge Institute, University of Southern California, Los Angeles, CA 90007, USADepartment of Biology, Rio Piedras Campus, University of Puerto Rico, San Juan 00931, Puerto RicoSince their discovery, nicotinic acetylcholine receptors (nAChRs) have been extensively studied to understand their function, as well as the consequence of alterations leading to disease states. Importantly, these receptors represent pharmacological targets to treat a number of neurological and neurodegenerative disorders. Nevertheless, their therapeutic value has been limited by the absence of high-resolution structures that allow for the design of more specific and effective drugs. This article offers a comprehensive review of five decades of research pursuing high-resolution structures of nAChRs. We provide a historical perspective, from initial structural studies to the most recent X-ray and cryogenic electron microscopy (Cryo-EM) nAChR structures. We also discuss the most relevant structural features that emerged from these studies, as well as perspectives in the field.https://www.mdpi.com/1420-3049/26/19/5753nicotinic acetylcholine receptorsligand-gated ion channel<i>Torpedo californica</i><i>Torpedo marmorata</i>cryogenic electron microscopycrystal structure |
| spellingShingle | Manuel Delgado-Vélez Orestes Quesada Juan C. Villalobos-Santos Rafael Maldonado-Hernández Guillermo Asmar-Rovira Raymond C. Stevens José Antonio Lasalde-Dominicci Pursuing High-Resolution Structures of Nicotinic Acetylcholine Receptors: Lessons Learned from Five Decades Molecules nicotinic acetylcholine receptors ligand-gated ion channel <i>Torpedo californica</i> <i>Torpedo marmorata</i> cryogenic electron microscopy crystal structure |
| title | Pursuing High-Resolution Structures of Nicotinic Acetylcholine Receptors: Lessons Learned from Five Decades |
| title_full | Pursuing High-Resolution Structures of Nicotinic Acetylcholine Receptors: Lessons Learned from Five Decades |
| title_fullStr | Pursuing High-Resolution Structures of Nicotinic Acetylcholine Receptors: Lessons Learned from Five Decades |
| title_full_unstemmed | Pursuing High-Resolution Structures of Nicotinic Acetylcholine Receptors: Lessons Learned from Five Decades |
| title_short | Pursuing High-Resolution Structures of Nicotinic Acetylcholine Receptors: Lessons Learned from Five Decades |
| title_sort | pursuing high resolution structures of nicotinic acetylcholine receptors lessons learned from five decades |
| topic | nicotinic acetylcholine receptors ligand-gated ion channel <i>Torpedo californica</i> <i>Torpedo marmorata</i> cryogenic electron microscopy crystal structure |
| url | https://www.mdpi.com/1420-3049/26/19/5753 |
| work_keys_str_mv | AT manueldelgadovelez pursuinghighresolutionstructuresofnicotinicacetylcholinereceptorslessonslearnedfromfivedecades AT orestesquesada pursuinghighresolutionstructuresofnicotinicacetylcholinereceptorslessonslearnedfromfivedecades AT juancvillalobossantos pursuinghighresolutionstructuresofnicotinicacetylcholinereceptorslessonslearnedfromfivedecades AT rafaelmaldonadohernandez pursuinghighresolutionstructuresofnicotinicacetylcholinereceptorslessonslearnedfromfivedecades AT guillermoasmarrovira pursuinghighresolutionstructuresofnicotinicacetylcholinereceptorslessonslearnedfromfivedecades AT raymondcstevens pursuinghighresolutionstructuresofnicotinicacetylcholinereceptorslessonslearnedfromfivedecades AT joseantoniolasaldedominicci pursuinghighresolutionstructuresofnicotinicacetylcholinereceptorslessonslearnedfromfivedecades |