Abstract
C2 domains are widespread Ca2+-binding modules. The active zone protein Piccolo (also known as Aczonin) contains an unusual C 2A domain that exhibits a low affinity for Ca2+, a Ca 2+-induced conformational change and Ca2+-dependent dimerization. We show here that removal of a nine-residue sequence by alternative splicing increases the Ca2+ affinity, abolishes the conformational change and abrogates dimerization of the Piccolo C2A domain. The NMR structure of the Ca2+-free long variant provides a structural basis for these different properties of the two splice forms, showing that the nine-residue sequence forms a β-strand otherwise occupied by a nonspliced sequence. Consequently, Ca2+-binding to the long Piccolo C2A domain requires a marked rearrangement of secondary structure that cannot occur for the short variant. These results reveal a novel mechanism of action of C2 domains and uncover a structural principle that may underlie the alteration of protein function by short alternatively spliced sequences.
Original language | English (US) |
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Pages (from-to) | 45-53 |
Number of pages | 9 |
Journal | Nature Structural and Molecular Biology |
Volume | 11 |
Issue number | 1 |
DOIs | |
State | Published - Jan 2004 |
ASJC Scopus subject areas
- Structural Biology
- Molecular Biology