期刊
NATURE STRUCTURAL & MOLECULAR BIOLOGY
卷 11, 期 1, 页码 45-53出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nsmb707
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资金
- NINDS NIH HHS [NS40944] Funding Source: Medline
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [R01NS040944] Funding Source: NIH RePORTER
C-2 domains are widespread Ca2+-binding modules. The active zone protein Piccolo ( also known as Aczonin) contains an unusual C(2)A 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 C(2)A 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 C(2)A domain requires a marked rearrangement of secondary structure that cannot occur for the short variant. These results reveal a novel mechanism of action of C-2 domains and uncover a structural principle that may underlie the alteration of protein function by short alternatively spliced sequences.
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