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PDBsum entry 4ns0
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Protein transport
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PDB id
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4ns0
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References listed in PDB file
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Key reference
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Title
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Structural insights into the ca2+ and pi(4,5)p2 binding modes of the c2 domains of rabphilin 3a and synaptotagmin 1.
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Authors
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J.Guillén,
C.Ferrer-Orta,
M.Buxaderas,
D.Pérez-Sánchez,
M.Guerrero-Valero,
G.Luengo-Gil,
J.Pous,
P.Guerra,
J.C.Gómez-Fernández,
N.Verdaguer,
S.Corbalán-García.
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Ref.
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Proc Natl Acad Sci U S A, 2013,
110,
20503-20508.
[DOI no: ]
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PubMed id
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Abstract
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Proteins containing C2 domains are the sensors for Ca(2+) and PI(4,5)P2 in a
myriad of secretory pathways. Here, the use of a free-mounting system has
enabled us to capture an intermediate state of Ca(2+) binding to the C2A domain
of rabphilin 3A that suggests a different mechanism of ion interaction. We have
also determined the structure of this domain in complex with PI(4,5)P2 and IP3
at resolutions of 1.75 and 1.9 Å, respectively, unveiling that the polybasic
cluster formed by strands β3-β4 is involved in the interaction with the
phosphoinositides. A comparative study demonstrates that the C2A domain is
highly specific for PI(4,5)P2/PI(3,4,5)P3, whereas the C2B domain cannot
discriminate among any of the diphosphorylated forms. Structural comparisons
between C2A domains of rabphilin 3A and synaptotagmin 1 indicated the presence
of a key glutamic residue in the polybasic cluster of synaptotagmin 1 that
abolishes the interaction with PI(4,5)P2. Together, these results provide a
structural explanation for the ability of different C2 domains to pull plasma
and vesicle membranes close together in a Ca(2+)-dependent manner and reveal how
this family of proteins can use subtle structural changes to modulate their
sensitivity and specificity to various cellular signals.
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