1rh8
Three-dimensional structure of the calcium-free Piccolo C2A-domain
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OverviewOverview
C2 domains are widespread Ca2+-binding modules. The active zone protein Piccolo (also known as Aczonin) contains an unusual C2A domain that exhibits a low affinity for Ca2+, a Ca2+-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 beta-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.
About this StructureAbout this Structure
1RH8 is a Single protein structure of sequence from Rattus norvegicus. Full crystallographic information is available from OCA.
ReferenceReference
A conformational switch in the Piccolo C2A domain regulated by alternative splicing., Garcia J, Gerber SH, Sugita S, Sudhof TC, Rizo J, Nat Struct Mol Biol. 2004 Jan;11(1):45-53. Epub 2003 Dec 29. PMID:14718922
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