1RH8
Three-dimensional structure of the calcium-free Piccolo C2A-domain
Summary for 1RH8
| Entry DOI | 10.2210/pdb1rh8/pdb |
| Descriptor | Piccolo protein (1 entity in total) |
| Functional Keywords | beta-sandwich, metal binding protein |
| Biological source | Rattus norvegicus (Norway rat) |
| Cellular location | Cell junction, synapse: Q9JKS6 |
| Total number of polymer chains | 1 |
| Total formula weight | 16479.60 |
| Authors | Garcia, J.,Gerber, S.H.,Sugita, S.,Sudhof, T.C.,Rizo, J. (deposition date: 2003-11-14, release date: 2004-01-13, Last modification date: 2024-05-22) |
| Primary citation | Garcia, J.,Gerber, S.H.,Sugita, S.,Sudhof, T.C.,Rizo, J. A conformational switch in the Piccolo C2A domain regulated by alternative splicing. Nat.Struct.Mol.Biol., 11:45-53, 2004 Cited by PubMed Abstract: 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. PubMed: 14718922DOI: 10.1038/nsmb707 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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