The Structural Versatility of the BTB Domains of KCTD Proteins and Their Recognition of the GABA<sub>B</sub> Receptor
Several recent investigations have demonstrated that members of the KCTD (Potassium Channel Tetramerization Domain) protein family are involved in fundamental processes. However, the paucity of structural data available on these proteins has frequently prevented the definition of their biochemical r...
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| Format: | Article |
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MDPI AG
2019-07-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/9/8/323 |
| _version_ | 1818294630327779328 |
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| author | Nicole Balasco Giovanni Smaldone Luigi Vitagliano |
| author_facet | Nicole Balasco Giovanni Smaldone Luigi Vitagliano |
| author_sort | Nicole Balasco |
| collection | DOAJ |
| description | Several recent investigations have demonstrated that members of the KCTD (Potassium Channel Tetramerization Domain) protein family are involved in fundamental processes. However, the paucity of structural data available on these proteins has frequently prevented the definition of their biochemical role(s). Fortunately, this scenario is rapidly changing as, in very recent years, several crystallographic structures have been reported. Although these investigations have provided very important insights into the function of KCTDs, they have also raised some puzzling issues. One is related to the observation that the BTB (broad-complex, tramtrack, and bric-à-brac) domain of these proteins presents a remarkable structural versatility, being able to adopt a variety of oligomeric states. To gain insights into this intriguing aspect, we performed extensive molecular dynamics simulations on several BTB domains of KCTD proteins in different oligomeric states (monomers, dimers, tetramers, and open/close pentamers). These studies indicate that KCTD-BTB domains are stable in the simulation timescales, even in their monomeric forms. Moreover, simulations also show that the dynamic behavior of open pentameric states is strictly related to their functional roles and that different KCTDs may form stable hetero-oligomers. Molecular dynamics (MD) simulations also provided a dynamic view of the complex formed by KCTD16 and the GABA<sub>B2</sub> receptor, whose structure has been recently reported. Finally, simulations carried out on the isolated fragment of the GABA<sub>B2</sub> receptor that binds KCTD16 indicate that it is able to assume the local conformation required for the binding to KCTD. |
| first_indexed | 2024-12-13T03:34:48Z |
| format | Article |
| id | doaj.art-c22773f83ca14ad58ceb261bbdafabc1 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-12-13T03:34:48Z |
| publishDate | 2019-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-c22773f83ca14ad58ceb261bbdafabc12022-12-22T00:01:04ZengMDPI AGBiomolecules2218-273X2019-07-019832310.3390/biom9080323biom9080323The Structural Versatility of the BTB Domains of KCTD Proteins and Their Recognition of the GABA<sub>B</sub> ReceptorNicole Balasco0Giovanni Smaldone1Luigi Vitagliano2Institute of Biostructures and Bioimaging, CNR, Via Mezzocannone 16, 80134 Napoli, ItalyIRCCS SDN, Via Gianturco 113, 80143 Napoli, ItalyInstitute of Biostructures and Bioimaging, CNR, Via Mezzocannone 16, 80134 Napoli, ItalySeveral recent investigations have demonstrated that members of the KCTD (Potassium Channel Tetramerization Domain) protein family are involved in fundamental processes. However, the paucity of structural data available on these proteins has frequently prevented the definition of their biochemical role(s). Fortunately, this scenario is rapidly changing as, in very recent years, several crystallographic structures have been reported. Although these investigations have provided very important insights into the function of KCTDs, they have also raised some puzzling issues. One is related to the observation that the BTB (broad-complex, tramtrack, and bric-à-brac) domain of these proteins presents a remarkable structural versatility, being able to adopt a variety of oligomeric states. To gain insights into this intriguing aspect, we performed extensive molecular dynamics simulations on several BTB domains of KCTD proteins in different oligomeric states (monomers, dimers, tetramers, and open/close pentamers). These studies indicate that KCTD-BTB domains are stable in the simulation timescales, even in their monomeric forms. Moreover, simulations also show that the dynamic behavior of open pentameric states is strictly related to their functional roles and that different KCTDs may form stable hetero-oligomers. Molecular dynamics (MD) simulations also provided a dynamic view of the complex formed by KCTD16 and the GABA<sub>B2</sub> receptor, whose structure has been recently reported. Finally, simulations carried out on the isolated fragment of the GABA<sub>B2</sub> receptor that binds KCTD16 indicate that it is able to assume the local conformation required for the binding to KCTD.https://www.mdpi.com/2218-273X/9/8/323oligomerizationmolecular dynamics simulationsprotein–protein interactions |
| spellingShingle | Nicole Balasco Giovanni Smaldone Luigi Vitagliano The Structural Versatility of the BTB Domains of KCTD Proteins and Their Recognition of the GABA<sub>B</sub> Receptor Biomolecules oligomerization molecular dynamics simulations protein–protein interactions |
| title | The Structural Versatility of the BTB Domains of KCTD Proteins and Their Recognition of the GABA<sub>B</sub> Receptor |
| title_full | The Structural Versatility of the BTB Domains of KCTD Proteins and Their Recognition of the GABA<sub>B</sub> Receptor |
| title_fullStr | The Structural Versatility of the BTB Domains of KCTD Proteins and Their Recognition of the GABA<sub>B</sub> Receptor |
| title_full_unstemmed | The Structural Versatility of the BTB Domains of KCTD Proteins and Their Recognition of the GABA<sub>B</sub> Receptor |
| title_short | The Structural Versatility of the BTB Domains of KCTD Proteins and Their Recognition of the GABA<sub>B</sub> Receptor |
| title_sort | structural versatility of the btb domains of kctd proteins and their recognition of the gaba sub b sub receptor |
| topic | oligomerization molecular dynamics simulations protein–protein interactions |
| url | https://www.mdpi.com/2218-273X/9/8/323 |
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