Sequence Analysis and Modeling of the Repetitive Region of the Long Isoform of Clarinet/CLA-1

The C. elegans active zone gene cla-1 encodes three main isoforms. The long isoform, CLA-1 L, functions beyond regulating synaptic vesicle exocytosis, including synaptic vesicle clustering and endocytic sorting of a transmembrane autophagy protein. CLA-1 L contains a large N-terminal repetitive region. Sequence analysis indicates that this region is enriched with acidic residues and displays disordered structures interspersed with helical sections. While modeling a portion of the repetitive region revealed dynamic transitions between compact and less compact conformations, modeling the entire region suggests a predominantly extended structure. This study sheds light on how CLA-1 L carries out its diverse functions.