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Three-dimensional structure of the calcium-free Piccolo C2A-domainThree-dimensional structure of the calcium-free Piccolo C2A-domain
Structural highlights
FunctionPCLO_RAT May act as a scaffolding protein involved in the organization of synaptic active zones and in synaptic vesicle trafficking (By similarity).[UniProtKB:Q9QYX7] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedC2 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. 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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