4NP9

Structure of Rabphilin C2A domain bound to IP3

Summary for 4NP9

• Entry DOI: 10.2210/pdb4np9/pdb
• Related: 2CHD 2CM5 2CM6 2K3H 4NS0
• Descriptor: Rabphilin-3A, D-MYO-INOSITOL-1,4,5-TRIPHOSPHATE, SULFATE ION, ... (4 entities in total)
• Functional Keywords: rabphilin-3a, c2 domain, c2a, calcium binding, synaptic exocytosis metal-binding, protein transport, c-2 domain fold, exophilin-1
• Biological source: Rattus norvegicus (brown rat,rat,rats)
• Cellular location: Cell junction, synapse (By similarity): P47709
• Total number of polymer chains: 1
• Total formula weight: 15821.64

Authors

Guillen, J.,Ferrer-Orta, C.,Buxaderas, M.,Perez-Sanchez, D.,Guerrero-Valero, M.,Luengo-Gil, G.,Pous, J.,Guerra, P.,Gomez-Fernandez, J.C.,Verdaguer, N.,Corbalan-Garcia, S. (deposition date: 2013-11-21, release date: 2013-12-25, Last modification date: 2024-05-29)

Primary citation

Guillen, J.,Ferrer-Orta, C.,Buxaderas, M.,Perez-Sanchez, D.,Guerrero-Valero, M.,Luengo-Gil, G.,Pous, J.,Guerra, P.,Gomez-Fernandez, J.C.,Verdaguer, N.,Corbalan-Garcia, S.
Structural insights into the Ca2+ and PI(4,5)P2 binding modes of the C2 domains of rabphilin 3A and synaptotagmin 1.
Proc.Natl.Acad.Sci.USA, 110:20503-20508, 2013

PubMed Abstract: 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.

PubMed: 24302762
DOI: 10.1073/pnas.1316179110

Experimental method

X-RAY DIFFRACTION (1.92 Å)