Work

The accessory helix of complexin functions by stabilizing central helix secondary structure

Year: 2014

Type: article

Abstract: 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.

Source: eLife

DOI: 10.7554/elife.04553

Authors: Daniel T Radoff, Yongming Dong, David Snead, Jihong Bai, David Eliezer, Jeremy S Dittman

Institutions: Weill Cornell Medicine, Fred Hutch Cancer Center

Language: English

Topic: Cellular transport and secretion

Subfield: Cell Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: gold

Estimated APC paid: $2,500