The accessory helix of complexin functions by stabilizing central helix secondary structure
The presynaptic protein complexin (CPX) is a critical regulator of synaptic vesicle fusion, but the mechanisms underlying its regulatory effects are not well understood. Its highly conserved central helix (CH) directly binds the ternary SNARE complex and is required for all known CPX functions. The...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2014-11-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/04553 |
| _version_ | 1811253378626355200 |
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| author | Daniel T Radoff Yongming Dong David Snead Jihong Bai David Eliezer Jeremy S Dittman |
| author_facet | Daniel T Radoff Yongming Dong David Snead Jihong Bai David Eliezer Jeremy S Dittman |
| author_sort | Daniel T Radoff |
| collection | DOAJ |
| description | The presynaptic protein complexin (CPX) is a critical regulator of synaptic vesicle fusion, but the mechanisms underlying its regulatory effects are not well understood. Its highly conserved central helix (CH) directly binds the ternary SNARE complex and is required for all known CPX functions. The adjacent accessory helix (AH) is not conserved despite also playing an important role in CPX function, and numerous models for its mechanism have been proposed. We examined the impact of AH mutations and chimeras on CPX function in vivo and in vitro using C. elegans. The mouse AH fully restored function when substituted into worm CPX suggesting its mechanism is evolutionarily conserved. CPX inhibitory function was impaired when helix propagation into the CH was disrupted whereas replacing the AH with a non-native helical sequence restored CPX function. We propose that the AH operates by stabilizing CH secondary structure rather than through protein or lipid interactions. |
| first_indexed | 2024-04-12T16:50:00Z |
| format | Article |
| id | doaj.art-7e8d9e91972044a29909d61497abf177 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T16:50:00Z |
| publishDate | 2014-11-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-7e8d9e91972044a29909d61497abf1772022-12-22T03:24:25ZengeLife Sciences Publications LtdeLife2050-084X2014-11-01310.7554/eLife.04553The accessory helix of complexin functions by stabilizing central helix secondary structureDaniel T Radoff0Yongming Dong1https://orcid.org/0000-0002-6510-0913David Snead2Jihong Bai3David Eliezer4https://orcid.org/0000-0002-1311-7537Jeremy S Dittman5Department of Biochemistry, Weill Cornell Medical College, New York, United StatesDivision of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, United StatesDepartment of Biochemistry, Weill Cornell Medical College, New York, United StatesDivision of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, United StatesDepartment of Biochemistry, Weill Cornell Medical College, New York, United StatesDepartment of Biochemistry, Weill Cornell Medical College, New York, United StatesThe presynaptic protein complexin (CPX) is a critical regulator of synaptic vesicle fusion, but the mechanisms underlying its regulatory effects are not well understood. Its highly conserved central helix (CH) directly binds the ternary SNARE complex and is required for all known CPX functions. The adjacent accessory helix (AH) is not conserved despite also playing an important role in CPX function, and numerous models for its mechanism have been proposed. We examined the impact of AH mutations and chimeras on CPX function in vivo and in vitro using C. elegans. The mouse AH fully restored function when substituted into worm CPX suggesting its mechanism is evolutionarily conserved. CPX inhibitory function was impaired when helix propagation into the CH was disrupted whereas replacing the AH with a non-native helical sequence restored CPX function. We propose that the AH operates by stabilizing CH secondary structure rather than through protein or lipid interactions.https://elifesciences.org/articles/04553complexinsynaptic transmissionexocytosisSNARE |
| spellingShingle | Daniel T Radoff Yongming Dong David Snead Jihong Bai David Eliezer Jeremy S Dittman The accessory helix of complexin functions by stabilizing central helix secondary structure eLife complexin synaptic transmission exocytosis SNARE |
| title | The accessory helix of complexin functions by stabilizing central helix secondary structure |
| title_full | The accessory helix of complexin functions by stabilizing central helix secondary structure |
| title_fullStr | The accessory helix of complexin functions by stabilizing central helix secondary structure |
| title_full_unstemmed | The accessory helix of complexin functions by stabilizing central helix secondary structure |
| title_short | The accessory helix of complexin functions by stabilizing central helix secondary structure |
| title_sort | accessory helix of complexin functions by stabilizing central helix secondary structure |
| topic | complexin synaptic transmission exocytosis SNARE |
| url | https://elifesciences.org/articles/04553 |
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