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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
2004-1-13
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pubmed:databankReference |
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pubmed:abstractText |
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.
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pubmed:grant |
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pubmed:commentsCorrections |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
1545-9993
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
11
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
45-53
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:14718922-Alternative Splicing,
pubmed-meshheading:14718922-Amino Acid Sequence,
pubmed-meshheading:14718922-Animals,
pubmed-meshheading:14718922-Binding Sites,
pubmed-meshheading:14718922-Calcium,
pubmed-meshheading:14718922-Calcium-Binding Proteins,
pubmed-meshheading:14718922-Cytoskeletal Proteins,
pubmed-meshheading:14718922-Membrane Glycoproteins,
pubmed-meshheading:14718922-Models, Molecular,
pubmed-meshheading:14718922-Molecular Sequence Data,
pubmed-meshheading:14718922-Nerve Tissue Proteins,
pubmed-meshheading:14718922-Neuropeptides,
pubmed-meshheading:14718922-Nuclear Magnetic Resonance, Biomolecular,
pubmed-meshheading:14718922-Protein Conformation,
pubmed-meshheading:14718922-Protein Structure, Tertiary,
pubmed-meshheading:14718922-Rats,
pubmed-meshheading:14718922-Recombinant Fusion Proteins,
pubmed-meshheading:14718922-Sequence Homology, Amino Acid,
pubmed-meshheading:14718922-Synaptotagmins
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pubmed:year |
2004
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pubmed:articleTitle |
A conformational switch in the Piccolo C2A domain regulated by alternative splicing.
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pubmed:affiliation |
Department of Biochemistry and Pharmacology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390, USA.
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pubmed:publicationType |
Journal Article,
In Vitro,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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