4LT7

Crystal structure of the c2a domain of rabphilin-3a in complex with a calcium

4LT7 の概要

• エントリーDOI: 10.2210/pdb4lt7/pdb
• 関連するPDBエントリー: 2CHD 2CM5 2CM6 2K3H
• 分子名称: Rabphilin-3A, CALCIUM ION (3 entities in total)
• 機能のキーワード: calcium binding, c2 domain, signal transduction, protein transport
• 由来する生物種: Rattus norvegicus (brown rat,rat,rats)
• 細胞内の位置: Cell junction, synapse : P47709
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 15345.56

構造登録者

Verdaguer, N.,Ferrer-Orta, C.,Buxaderas, M.,Corbalan-Garcia, S.,Perez-Sanchez, D.,Guerrero-Valero, M.,Luengo, G.,Pous, J.,Guerra, P.,Gomez-Fernandez, J.C.,Guillen, J. (登録日: 2013-07-23, 公開日: 2013-12-11, 最終更新日: 2023-09-20)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.5 Å)